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User’s Guide

Chem & Bio Office Desktop 2008 for Windows

Chem & Bio Ofﬁce is an integrated suite including: • Chem & Bio Draw for chemical and pathway drawing • Chem & Bio 3D for molecular modeling and analysis • ChemFinder for searching and information integration • BioAssay & BioVIz for biological data retrieval and visualization • Inventory for managing and searching reagents, • E-Notebook for electronic journal and information • ChemInfo for chemical and scientific databases

Chem & Bio Office® Chem & Bio 3D, Finder and BioViz

License Information

ChemOffice, BioOffice ChemDraw, Chem3D, ChemINDEX, ChemFinder, and ChemInfo programs, all resources in the ChemOffice, ChemDraw, Chem3D, ChemFinder, and ChemInfo application files, and this manual are Copyright © 1986-2006 by CambridgeSoft Corporation (CS) with all rights reserved worldwide. MOPAC 2002 is Copyright © 1993-2006 by Fujitsu Limited with all rights reserved. Information in this document is subject to change without notice and does not represent a commitment on the part of CS. Both these materials and the right to use them are owned exclusively by CS. Use of these materials is licensed by CS under the terms of a software license agreement; they may be used only as provided for in said agreement.

ChemOfﬁce, ChemDraw, Chem3D, CS MOPAC, ChemFinder, Inventory, E-Notebook, BioAssay, and ChemInfo are not supplied with copy protection. Do not duplicate any of the copyrighted materials except for your personal backups without written permission from CS. To do so would be in violation of federal and international law, and may result in criminal as well as civil penalties. You may use ChemOfﬁce, ChemDraw, Chem3D, CS MOPAC, ChemFinder, Inventory, E-Notebook, BioAssay, and ChemInfo on any computer owned by you; however, extra copies may not be made for that purpose. Consult the CS License Agreement for Software and Database Products for further details.

Trademarks

ChemOfﬁce, BioOffice, ChemDraw, Chem3D, ChemINDEX, ChemFinder, ChemInfo and ChemACX are registered trademarks of CambridgeSoft Corporation (Cambridge Scientiﬁc Computing, Inc.).

MOPAC 2002 is a trademark of Fujitsu Limited.

Microsoft Windows, Windows 2000, Windows XP, and Microsoft Word are registered trademarks of Microsoft Corp.

Apple Events, Macintosh, Laserwriter, Imagewriter, QuickDraw and AppleScript are registered trademarks of Apple Computer, Inc. Geneva, Monaco, and TrueType are trademarks of Apple Computer, Inc.

The ChemSelect Reaction Database is copyrighted © by InfoChem GmbH 1997.

AspTear is copyrighted © by Softwing.

InChI™ is a trademark of the International Union of Pure and Applied Chemistry. InChI™ Material in ChemDraw is © IUPAC 2005.

SCHRÖDINGER® Jaguar

GAMESS is copyrighted © by Ames Laboratory

All other trademarks are the property of their respective holders. CambridgeSoft End-User License Agreement for Software Products

Important: This CambridgeSoft Software License Agreement (“Agreement”) is a legal agreement between you, the end user (either an individual or an entity), and CambridgeSoft Corporation (“CS”) regarding the use of CS Software Products, which may include computer software, the associated media, any printed materials, and any “online” or electronic documentation. By installing, copying, or otherwise using any CS Software Product, you signify that you have read the CS End User License Agreement and agree to be bound by its terms. If you do not agree to the Agreement’s terms, promptly return the package and all its contents to the place of purchase for a full refund.

CambridgeSoft Software License

1. Grant of License. CambridgeSoft (CS) Software Products are licensed, not sold. CS grants and you hereby accept a nonexclusive license to use one copy of the enclosed Software Product (“Software”) in accordance with the terms of this Agreement. This licensed copy of the Software may only be used on a single computer, except as provided below. You may physically transfer the Software from one computer to another for your own use, provided the Software is in use (or installed) on only one computer at a time. If the Software is permanently installed on your computer (other than a network server), you may also use the Software on a portable or home computer, provided that you use the software on only one computer at a time. You may not (a) electronically transfer the Software from one computer to another, (b) distribute copies of the Software to others, or (c) modify or translate the Software without the prior written consent of CS, (d) place the software on a server so that it is accessible via a public network such as the Internet, (e) sublicense, rent, lease or lend any portion of the Software or Documentation, (f) modify or adapt the Software or merge it into another program, (g) modify or circumvent the software activation, or (h) reverse engineer the software activation so as to circumvent it. The Software may be placed on a file or disk server connected to a network, provided that a license has been purchased for every computer with access to that server. You may make only those copies of the Software which are necessary to install and use it as permitted by this agreement, or are for purposes of backup and archival records; all copies shall bear CS’s copyright and proprietary notices. You may not make copies of any accompanying written materials.

With a fixed license, the software cannot be installed on more than the number of computers equivalent to the number of fixed licenses purchased. For example, a 10-user fixed license means the software can be installed on no more than 10 different computers. A fixed license cannot be installed on a server. With a concurrent license, the software can be installed on any number of computers at the organization, but the number of computers using the software at any one time cannot exceed the number of concurrent licenses purchased. For example, a 10-user concurrent license can be installed on 20 computers, but no more than 10 users can be using it at any one time. If the number of users of the software could potentially exceed the number of licensed copies, then Licensee must have a reasonable mechanism or process in place to assure that the number of persons using the software does not exceed the number of copies. CambridgeSoft reserves the right to conduct periodic audits no more than once per year to review the implementation of this agreement at the Licensee’s site. At CambridgeSoft’s request, Licensee will provide a knowledgeable employee to assist in said audit

2. Ownership. The Software is and at all times shall remain the sole property of CS. This ownership is protected by the copyright laws of the United States and by international treaty provisions. Upon expiration or termination of this agreement, you shall promptly return all copies of the Software and accompanying written materials to CS. You may not modify, decompile, reverse engineer, or disassemble the Software.

3. Assignment Restrictions. You may not rent, lease, or otherwise sublet the Software or any part thereof. You may transfer on a permanent basis the rights granted under this license provided you transfer this Agreement and all copies of the Software, including prior versions, and all accompanying materials. The recipient must agree to the terms of this Agreement in full and register this transfer in writing with CS. 4. Use of Included Data. All title and copyrights in and to the Software product, including but not limited to any images, photographs, animations, video, audio, music, text, applets, Java applets, and data files and databases (the “Included Data”), are owned by CS or its suppliers.

· You may not copy, distribute or otherwise make the Included Data publicly available.

· Licensed users of ChemOffice Enterprise and Workgroup and the accompanying Plugin software products may access, search, and view the Included Data and may transmit the results of any search of the Included Data to other users of the licensed ChemOffice Enterprise and Workgroup software products within your organization only, provided that such transmission is via an internal corporate (or university) network and is not accessible by the public.

· You may not install the Included Data on non-licensed computers nor distribute or otherwise make the Included Data publicly available.

· You may use the Software to organize personal data, and you may transmit such personal data over the Internet provided that the transmission does not contain any Included Data.

· All rights not specifically granted under this Agreement are reserved by CS.

5. Separation of Components. The Software is licensed as a single product. Its component parts may not be separated for use on more than one computer, except in the case of ChemOffice Enterprise. ChemOffice Enterprise includes licenses for ChemDraw ActiveX and licenses for Chem3D ActiveX. The ActiveX software products may be installed on computers other than that one on which ChemOffice Enterprise is installed. However, each copy of the ActiveX is individually subject to the provisions of Paragraphs 1 through 4 of this Agreement.

6. Educational Use Only of Student Licenses. If you are a student enrolled at an educational institution, the CS License Agreement grants to you personally a license to use one copy of the enclosed Software in accordance with the terms of this Agreement. In this case the CS License Agreement does not permit commercial use of the Software nor does it permit you to allow any other person to use the Software.

7. Termination. You may terminate the license at any time by destroying all copies of the Software and documentation in your possession. Without prejudice to any other rights, CS may terminate this Agreement if you fail to comply with its terms and conditions. In such event, you must destroy all copies of the Software Product and all of its component parts.

8. Confidentiality. The Software contains trade secrets and proprietary know-how that belong to CS and are being made available to you in strict confidence. ANY USE OR DISCLOSURE OF THE SOFTWARE, OR USE OF ITS ALGORITHMS, PROTOCOLS OR INTERFACES, OTHER THAN IN STRICT ACCORDANCE WITH THIS LICENSE AGREEMENT, MAY BE ACTIONABLE AS A VIOLATION OF OUR TRADE SECRET RIGHTS.

CS Limited Warranty

Limited Warranty. CS’s sole warranty with respect to the Software is that it shall be free of errors in program logic or documentation, attributable to CS, which prevent the performance of the principal computing functions of the Software. CS warrants this for a period of thirty (30) days from the date of receipt. CS’s Liability. In no event shall CS be liable for any indirect, special, or consequential damages, such as, but not limited to, loss of anticipated profits or other economic loss in connection with or arising out of the use of the software by you or the services provided for in this agreement, even if CS has been advised of the possibility of such damages. CS’s entire liability and your exclusive remedy shall be, at CS’s discretion, either (A) return of any license fee, or (B) correction or replacement of software that does not meet the terms of this limited warranty and that is returned to CS with a copy of your purchase receipt. NO OTHER WARRANTIES. CS DISCLAIMS OTHER IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, AND IMPLIED WAR- RANTIES ARISING BY USAGE OF TRADE, COURSE OF DEALING, OR COURSE OF PERFORMANCE. NOTWITH- STANDING THE ABOVE, WHERE APPLICABLE, IF YOU QUALIFY AS A “CONSUMER” UNDER THE MAGNUSON- MOSS WARRANTY ACT, THEN YOU MAY BE ENTITLED TO ANY IMPLIED WARRANTIES ALLOWED BY LAW FOR THE PERIOD OF THE EXPRESS WARRANTY AS SET FORTH ABOVE. SOME STATES DO NOT ALLOW LIMITATIONS ON IMPLIED WARRANTIES, SO THE ABOVE LIMITATION MIGHT NOT APPLY TO YOU. THIS WARRANTY GIVES YOU SPECIFIC LEGAL RIGHTS, AND YOU MAY ALSO HAVE OTHER RIGHTS WHICH VARY FROM STATE TO STATE.

No Waiver. The failure of either party to assert a right hereunder or to insist upon compliance with any term or condition of this Agreement shall not constitute a waiver of that right or excuse a similar subsequent failure to perform any such term or condition by the other party.

Governing Law. This Agreement shall be construed according to the laws of the Commonwealth of Massachusetts.

Export. You agree that the Software will not be shipped, transferred, or exported into any country or used in any manner prohibited by the United States Export Administration Act or any other export laws, restrictions, or regulations.

End-User License Agreement for CambridgeSoft Database Products

Important: This CambridgeSoft End-User License Agreement is a legal agreement between you (either an individual or a single entity) and CambridgeSoft Corporation for the CambridgeSoft supplied database product(s) and may include associated media, printed materials, and “online” or electronic documentation. By using the database product(s) you agree that you have read, understood and will be bound by this license agreement.

Database Product License

1. Copyright Notice. The materials contained in CambridgeSoft Database Products, including but not limited to, ChemACX, ChemIndex, and The Merck Index, are protected by copyright laws and international copyright treaties, as well as other intellectual property laws and treaties. Copyright in the materials contained on the CD and internet subscription products, including, but not limited to, the textual material, chemical structures representations, artwork, photographs, computer software, audio and visual elements, is owned or controlled separately by CambridgeSoft Corporation (“CS”).

CS is a distributor (and not a publisher) of information supplied by third parties. Accordingly, CS has no editorial control over such information. Database Suppliers (“Supplier”) individually own all right, title, and interest, including copyright, in their database—and retain all such rights in providing information to Customers.

The materials contained in The Merck Index are protected by copyright laws and international copyright treaties, as well as other intellectual property laws and treaties. Copyright in the materials contained on the CD and internet subscription products, including, but not limited to, the textual material, chemical structures representations, artwork, photographs, computer software, audio and visual elements, is owned or controlled separately by the Merck & Co., Inc., (“Merck”) and CambridgeSoft Corporation (“CS”).

2. Limitations on Use. Except as expressly provided by copyright law, copying, redistribution, or publication, whether for commercial or non-commercial purposes, must be with the express permission of CS and/or Merck. In any copying, redistribution, or publication of copyrighted material, any changes to or deletion of author attribution or copyright notice, or any other proprietary notice of CS, Merck, or other Database producer are prohibited. 3. Grant of License, CD/DVD Databases. CambridgeSoft Software Products are licensed, not sold. CambridgeSoft grants and you hereby accept a nonexclusive license to use one copy of the enclosed Software Product (“Software”) in accordance with the terms of this Agreement. This licensed copy of the Software may only be used on a single computer, except as provided below. You may physically transfer the Software from one computer to another for your own use, provided the Software is in use (or installed) on only one computer at a time. If the Software is permanently installed on your computer (other than a network server), you may also use the Software on a portable or home computer, provided that you use the software on only one computer at a time. You may not (a) electronically transfer the Software from one computer to another, (b) distribute copies of the Software to others, or (c) modify or translate the Software without the prior written consent of CambridgeSoft, (d) place the software on a server so that it is accessible via a public network such as the Internet, (e) sublicense, rent, lease or lend any portion of the Software or Documentation, or (f ) modify or adapt the Software or merge it into another program. The Software may be placed on a file or disk server connected to a network, provided that a license has been purchased for every computer with access to that server. You may make only those copies of the Software which are necessary to install and use it as permitted by this agreement, or are for purposes of backup and archival records; all copies shall bear CambridgeSoft’s copyright and proprietary notices. You may not make copies of any accompanying written materials.

4. Assignment Restrictions for CD/DVD databases. You may not rent, lease, or otherwise sublet the Software or any part thereof. You may transfer on a permanent basis the rights granted under this license provided you transfer this Agreement and all copies of the Software, including prior versions, and all accompanying materials. The recipient must agree to the terms of this Agreement in full and register this transfer in writing with CambridgeSoft.

5. Revocation of Subscription Access. Any use which is commercial and/or non-personal is strictly prohibited, and may subject the Subscriber making such uses to revocation of access to this Paid Subscription Service, as well as any other applicable civil or criminal penalties. Similarly, sharing a Subscriber password with a non-Subscriber or otherwise making this Paid Subscription Service available to third parties other than the Authorized User as defined above is strictly prohibited, and may subject the Subscriber participating in such activities to revocation of access to the Paid Subscription Services; and, the Subscriber and any third party, to any other applicable civil or criminal penalties under copyright or other laws. In the case of an authorized site license, a Subscriber shall cause any employee, agent or other third party which the Subscriber allows to use the Paid Subscription Service materials to abide by all of the terms and conditions of this Agreement. In all other cases, only the Subscriber is permitted to access the Paid Subscription Service materials. Should CambridgeSoft become aware of any use that might cause revocation of the license, they shall notify the Subscriber. The Subscriber shall have 90 days from date of notice to correct such violation before any action will be taken.

6. Trademark Notice. THE MERCK INDEX ® is a trademark of Merck & Company Incorporated, Whitehouse Station, New Jersey, USA and is registered in the United States Patent and Trademark Office. CambridgeSoft ® and ChemACX are trademarks of CambridgeSoft Corporation, Cambridge,Massachusetts, USA and are registered in the United States Patent and Trademark Office, the European Union (CTM) and Japan.

Any use of the marks in connection with the sale, offering for sale, distribution or advertising of any goods and services, including any other website, or in connection with labels, signs, prints, packages, wrappers, receptacles or adver- tisements used for the sale, offering for sale, distribution or advertising of any goods and services, including any other website, which is likely to cause confusion, to cause mistake or to deceive, is strictly prohibited.

7. Modification of Databases, Websites, or Subscription Services. CS reserves the right to change, modify, sus- pend or discontinue any or all parts of any Paid Subscription Services and databases at any time. 8. Representations and Warranties. The User shall indemnify, defend and hold CS, Merck, and/or other Supplier harmless from any damages, expenses and costs (including reasonable attorneys’ fees) arising out of any breach or alleged breach of these Terms and Conditions, representations and/or warranties herein, by the User or any third party to whom User shares her/his password or otherwise makes available this Subscription Service. The User shall cooper- ate in the defense of any claim brought against CambridgeSoft, Merck, and/or other Database Suppliers.

In no event shall CS, Merck, and/or other Supplier be liable for any indirect, special, or consequential damages, such as, but not limited to, loss of anticipated profits or other economic loss in connection with or arising out of the use of the software by you or the services provided for in this agreement, even if CS, Merck, and/or other Supplier has been advised of the possibility of such damages. CS and/or Merck’s entire liability and your exclusive remedy shall be, at CS’s discretion a return of any pro-rata portion of the subscription fee.

The failure of either party to assert a right hereunder or to insist upon compliance with any term or condition of this Agreement shall not constitute a waiver of that right or excuse a similar subsequent failure to perform any such term or condition by the other party.

This Agreement shall be construed according to the laws of the Commonwealth of Massachusetts, United States of America.

: IS IT OK TO COPY MY COLLEAGUE’S Q: So I'm never allowed to copy software for any other SOFTWARE? reason? Q NO, it’s not okay to copy your colleague’s software. Software is protected by federal copyright law, A: That’s correct. Other than copying the software you which says that you can't make such additional copies purchase onto a single computer and making another without the permission of the copyright holder. By copy “for archival purposes only” or “purposes only of maintenance or repair,” the copyright law prohibits protecting the investment of computer software you from making additional copies of the software for companies in software development, the copyright law any other reason unless you obtain the permission of serves the cause of promoting broad public availability of the software company. new, creative, and innovative products. These companies devote large portions of their earnings to the creation of Q: At my company, we pass disks around all the time. new software products and they deserve a fair return on We all assume that this must be okay since it was their investment. The creative teams who develop the the company that purchased the software in the software–programmers, writers, graphic artists and first place. others–also deserve fair compensation for their efforts. Without the protection given by our copyright laws, they A: Many employees don’t realize that corporations are would be unable to produce the valuable programs that bound by the copyright laws, just like everyone else. have become so important to our daily lives: educational Such conduct exposes the company (and possibly the persons involved) to liability for copyright software that teaches us much needed skills; business infringement. Consequently, more and more software that allows us to save time, effort and money; corporations concerned about their liability have and entertainment and personal productivity software written policies against such “softlifting”. Employees that enhances leisure time. may face disciplinary action if they make extra copies of the company’s software for use at home or on Q: That makes sense, but what do I get out of additional computers within the office. A good rule to purchasing my own software? remember is that there must be one authorized copy of a software product for every computer upon which A: When you purchase authorized copies of software it is run programs, you receive user guides and tutorials, quick reference cards, the opportunity to purchase Q: Can I take a piece of software owned by my company and install it on my personal computer at upgrades, and technical support from the software home if instructed by my supervisor? publishers. For most software programs, you can read about user benefits in the registration brochure or A: A good rule of thumb to follow is one software upgrade flyer in the product box. package per computer, unless the terms of the license agreement allow for multiple use of the program. But Q: What exactly does the law say about copying some software publishers’ licenses allow for “remote” software? or “home” use of their software. If you travel or telecommute, you may be permitted to copy your A: The law says that anyone who purchases a copy of software onto a second machine for use when you are software has the right to load that copy onto a single not at your office computer. Check the license care- computer and to make another copy “for archival fully to see if you are allowed to do this. purposes only” or, in limited circumstances, for Q: What should I do if become aware of a company “purposes only of maintenance or repair.” It is illegal that is not compliant with the copyright law or its to use that software on more than one computer or to software licenses? make or distribute copies of that software for any other purpose unless specific permission has been A: Cases of retail, corporate and Internet piracy or non- obtained from the copyright owner. If you pirate compliance with software licenses can be reported on software, you may face not only a civil suit for the Internet at http://www.siia.net/piracy/report.asp damages and other relief, but criminal liability as well, or by calling the Anti-Piracy Hotline: including fines and jail terms of up to one year (800) 388-7478. Q: Do the same rules apply to bulletin boards and user SIIA also offers a number of other materials designed to groups? I always thought that the reason they got help you comply with the Federal Copyright Law. These together was to share software. materials include:

A: Yes. Bulletin boards and user groups are bound by the "It's Just Not Worth the Risk" video. copyright law just as individuals and corporations. This 12–minute video, available $10, has helped over However, to the extent they offer shareware or public 20,000 organizations dramatize to their employees the domain software, this is a perfectly acceptable implications and consequences of software piracy. practice. Similarly, some software companies offer bulletin boards and user groups special demonstration versions of their products, which in some instances “Don’t Copy that Floppy” video may be copied. In any event, it is the responsibility of This 9 minute rap video, available for $10, is designed the bulletin board operator or user group to respect to educate students on the ethical use of software. copyright law and to ensure that it is not used as a vehicle for unauthorized copying or distribution. Other education materials including, “Software Use Q: I'll bet most of the people who copy software don't and the Law”, a brochure detailing the copyright law even know that they're breaking the law. and how software should be used by educational institutions, corporations and individuals; and several A: Because the software industry is relatively new, and posters to help emphasize the message that unauthorized because copying software is so easy, many people are copying of software is illegal. either unaware of the laws governing software use or choose to ignore them. It is the responsibility of each To order any of these materials, please send your request to: and every software user to understand and adhere to copyright law. Ignorance of the law is no excuse. If “SIIA Anti-Piracy Materials” you are part of an organization, see what you an do to Software & Information Industry Association initiate a policy statement that everyone respects. 1090 Vermont Ave, Sixth Floor, Also, suggest that your management consider Washington, D.C. 20005 conducting a software audit. Finally, as an individual, (202) 289-7442 help spread the word that users should be “software legal.” We urge you to make as many copies as you would like in order to help us spread the word that unauthorized copying of software is illegal. Q: What are the penalties for copyright infringement?

A: The Copyright Act allows a copyright owner to recover monetary damages measured either by: (1) its actual damages plus any additional profits of the infringer attributable to the infringement, or (2) statutory damages, of up to $150,000 for each copyrighted work infringed. The copyright owner also has the right to permanently enjoin an infringer from engaging in further infringing activities and may be awarded costs and attorneys’ fees. The law also permits destruction or other reasonable disposition of all infringing copies and devices by which infringing copies have been made or used in violation of the copyright owner’s exclusive rights. In cases of willful infringement, criminal penalties may also be assessed against the infringer. A Guide to CambridgeSoft Manuals

Manuals: Chem & Bio Draw Chem & Bio Office Chem & Bio Office Chem & Bio Desktop Software Enterprise Solutions Drawing Standard Chem & Bio 3D and Databases Includes Finder & BioViz Including E-Notebook Chem & Bio Draw I Chem & Bio 3D I e r Chem & Bio Finder I a

w I t BioAssay Desktop f o I S BioViz Desktop Inventory Desktop I E-Notebook Desktop I

s ChemDraw/Excel I n o i I t Struct = Name a c i I

l ChemNMR p p CombiChem/Excel I A

p ChemFinder/Office I o t k I

s MOPAC, GAMESS, MM2 e

D CS Gaussian, Jaguar Interface I

Chem & Bio Office Enterprise, WorkGroup I E-Notebook Enterprise, Workgroup I CombiChem/E-Notebook I s n Workflow LIMS I o i t I u DocManager Enterprise l o

S BioAssay Enterprise, Workgroup I e s i BioSAR Enterprise I r p r Inventory Enterprise, Workgroup I e t n I E Registration Enterprise Formulations & Mixtures I Compliant DB I Oracle Cartridge I

The Merck Index I R&D Insight/Chemists I ChemINDEX Database, NCI, AIDS & Cancer I s e

s Traditional Chinese Medicines I a b Drugs: Synonyms & Properties I a t a Nanogens Index; Medicinal Chemistry I D ChemACX, ChemMSDS Database I Sigma-Aldrich MSDS I ChemReact500, ChemReact68 & ChemSynth I

Structure Drawing Tips I s p i Searching Tips I I I T Importing SD Files I Chem & Bio Office 2008

CambridgeSoft proudly introduces Chem & Bio been using to jot notes about interesting molecules Office 2008. This guide provides detailed informa- and reactions, but does it much better! With Chem- tion on three Chem & BioOffice applications– Finder, you can search through data efficiently and Chem & Bio 3D, ChemScript, and ChemFinder & quickly, and you can organize the data instantly. BioViz. Use this guide as a reference to each appli- ChemFinder & BioViz 11.0 is integrated with the cation’s features, commands. Section I describes following CambridgeSoft products. Chem & Bio 3D 11.0. Section II describes Chem- Script. Section III describes ChemFinder & Bioviz. • Chem & Bio Draw 11.0 • Chem & Bio 3D 11.0 About Chem & Bio 3D 11.0 • ChemDraw/Excel Chem & Bio 3D is a chemical modeling tool. It •ChemFinder/Office combines powerful building, analysis, and calcula- Use the BioViz add-in to better visualize your data. tion tools with easy-to use graphical user interface, With BioViz, you can create a variety of data plots and a powerful scripting interface. viewing them directly in ChemFinder without the Chem & Bio 3D provides computational tools need for another application. based on molecular mechanics for optimizing models, conformational searching, molecular About ChemFinder/Office dynamics, and calculating single point energies for ChemFinder/Office helps you to build databases molecules. by extracting information from various sources. About ChemScript With ChemFinder/Office, you can browse Word documents or Excel spreadsheets to find chemical CambridgeSoft introduces ChemScript to the databases and ChemDraw, Isis/Draw, or SD files. ChemOffice 11.0 family of products. ChemScript In addition to browsing, ChemFinder/Office can is a library of program algorithms used in many search these files by chemical structure or formula, CambridgeSoft applications. These scripts are now or by molecular weight. available for you to customize to fit the way you work. If you are familiar with the Python language, About this Guide you will find customizing the scripts quite easy. CambridgeSoft makes Python available with This manual contains information for the Chem & ChemScript, so you can get started right away. Bio Office 2008 desktop applications. It assumes you are familiar with the basics of you operating About ChemFinder & BioViz system. If you are not, refer to your system manual. Some of the material describes tasks that must be ChemFinder is a database management system, a performed in conjunction with Microsoft Excel or powerful tool for anyone who works with chemical Word. If needed, refer to the users’s manual for information. It provides a place to store chemical these applications. structures, physical properties, notes, and data. It takes the place of that box of index cards you’ve

Chem & Bio Office 2008: Chem & Bio 3D, ChemScript, and ChemFinder & BioViz i User Guide The lower left cornerThe of the applica- lower A brief description of an object that Available in the Help menu for each Chem Chem each for in the Help menu Available CambridgeSoft Web site CambridgeSoft Web for more information sites below on Web the See CambridgeSoft products: Support Technical http://www.cambridgesoft.com/services ChemDraw Plugin http://www.cambridgesoft.com/services/documentation/chemdrawplugin/ Chem3D ActiveX control http://www.cambridgesoft.com/services/Desk- topSupport/Documentation/Chem3DControl/ Kit Developer’s Software http://sdk.cambridgesoft.com/ chemicals and products Purchasing http://scistore.cambridgesoft.com/ Quick Reference Cards Reference Quick back are located in the Cars Reference The Quick The cards manual. & Bio Office 2008 of the Chem summariesapplication of desktopprovide com- instruc-of the many Because and features. mands require knowledge of the interface elements, tions perform you as cards the Reference Quick the us tutorials. Online Help 2008applications provide Chem & Bio Office types of Help: following the some or all of Help. application. 2008 & Bio Office Tips. Tool appearspoint when you to the object. Status Bar. useful informationdisplays that as window tion youwork. . Through menu, menu, and Through X-Y Through Structure you become familiar familiar become you Reflect Model , , and then select , and then Structure , are the action items in the in the items , are the action Structure>Reflect Model>Through X-Y Plane X-Y Model>Through Structure>Reflect Reflect Model . www.cambridgesoft.com/support. tion ii • site: The CambridgeSoftWeb • The reference cards ChemOffice Quick •applica- ChemOffice Thefor each Help system X-Y Plane Additional Information to the resources following Refer for more informa- to use ChemOfficetion on products how and them: Instructionsfind select orto willoften ask you Each or dialog box. items that are in either a menu is differenta font that inaction item appears from the regular text. select Action items Navigation to navigate through you will ask a task Typically, to reflectexample, For a items. menu various ofone model through Chem & Bio 3D X-Y plane, the stepsbe: will 1. Go to instructions dedicated is document this of to explaining Much basic Thereperformare two to how tasks. specific step. each follow you used to help conventions with the Chem & Bio Office applications so that applications so that & Bio Office with the Chem as possible. can beginquickly using them as you Conventions The notations throughout are used following this guide: The chapters in this guide are organized guide in this The task. chapters by Theyhelp to are intended This means that you start This means that you at the Plane

Administrator Microsoft® Office Products Draw 11.0 and Chem & Bio 3D 11.0 ActiveX controls. To activate them, you must choose the option to “allow ChemOffice products are compatible with the fol- blocked content” from the bar appearing under the address lowing versions of Microsoft Office: bar notifying you that the security settings have blocked some of the content of the page. Internet Explorer does not remem- System Requirements ber this information, so you must repeat the activation each Before installing Chem & BioDraw, see the “Read- time you access the page. MeFirst” and any other ReadMe documents on the If you visit a site frequently, you can add it to the list of installation CD-ROM. trusted sites in IE’s security settings. Windows® Requirements Macintosh® Requirements Operating System. Windows 2000, XP Pro (32- bit only), Windows Vista (32-bit only). Operating System. Mac OS X 10.3.x, Mac OS X Browsers. Microsoft Internet Explorer 7.x, 10.4 PowerPC, Mac OS X 10.4 Intel, Mac OS X Microsoft Internet Explorer 6.x, Firefox 1.x, 10.5 PowerPC/Intel. Netscape 7.x, Mozilla 1.x Browsers. Safari 1.4 and higher, Firefox 1.x, Microsoft Office. Microsoft Office 2000, Mozilla 1.7.5 and higher, Netscape 7.0.x Microsoft Office XP, Microsoft Office 2003 Screen Resolution. Chem & Bio 3D supports a Screen Resolution. Chem & Bio 3D supports a Macintosh screen resolution of 800 x 600 or PC screen resolution of 800 x 600 or higher. higher.

NOTE: Windows XP Service Pack 2 includes security features that automatically block active content. This means that by default, Internet Explorer blocks Chem & Bio

Chem & Bio Office 2008: Chem & Bio 3D, ChemScript, and ChemFinder & BioViz iii User Guide iv

Administrator Contents Chem & Bio Office 2008 Saving Models ...... 6 Preferences Dialog Box ...... 6 About Chem & Bio 3D 11.0 ...... i Menus and Toolbars ...... 7 About ChemScript ...... i Detaching toolbars ...... 7 About ChemFinder & BioViz ...... i The File Menu...... 7 About ChemFinder/Office ...... i The Edit Menu ...... 7 About this Guide ...... i The View Menu ...... 8 Conventions ...... ii The Structure Menu ...... 10 instructions ...... ii The Standard Toolbar ...... 12 Navigation ...... ii The Building Toolbar...... 12 Action items ...... ii The Model Display Toolbar...... 12 Additional Information ...... ii The Surfaces Toolbar...... 13 Quick Reference Cards ...... ii The Demo Toolbar...... 13 Online Help ...... ii The Calculation Toolbar ...... 14 CambridgeSoft Web site ...... ii The ChemDraw Panel ...... 14 Microsoft® Office Products ...... iii Linking windows ...... 14 System Requirements ...... iii Draw to 3D (Add and Replace) ...... 15 Windows® Requirements ...... iii 3D to Draw...... 15 Macintosh® Requirements ...... iii The Model Information Panel ...... 15 Output and Comments ...... 16 Exporting comments ...... 16 Model Building Basics ...... 16 Section I Internal and External Tables ...... 16 Chem & Bio3D 11.0 Viewing Options ...... 17 Standard Measurements ...... 17 About CS MOPAC ...... 1 Model Settings ...... 17 About Gaussian ...... 1 Model Display ...... 17 About Jaguar ...... 1 Model Data Labels...... 18 New in Chem & Bio 3D 11.0 ...... 3 Atom Types ...... 19 Chem3D Pro 11.0...... 3 Rectification...... 19 Bio3D Ultra 11.0 ...... 3 Bond Lengths and Bond Angles ...... 19 ChemBio3D Ultra 11.0 ...... 3 The Model Explorer ...... 19 Features ...... 3 Model Coordinates ...... 20 Support for Office 2007 ...... 4 Z-matrix ...... 20 Cartesian Coordinates ...... 20 Chapter 1 The Measurement Table ...... 20 Chem & Bio 3D 11.0 Basics ...... 5 Getting Around ...... 5 Chapter 2 The Model Window ...... 5 Tutorials ...... 23 Rotation Bars...... 6 Tutorial 1: The ChemDraw Panel ...... 23

Chem & Bio Office 2008: Chem & Bio 3D, ChemScript, and ChemFinder & BioViz v User Guide .... 56 ...... 57 ...... 57 ...... 53 ...... 47 ...... 56 ...... 56 ...... 47 ...... 50 ...... 59 ...... tion ...... 55 ...... ace ...... rfaces ...... ace ...... Setting Solid Sphere Size SettingTypes Molecular Surface ...... 54 SettingIsovalues...... Molecular Surface 55 Resolu Setting the Surface SettingColors Molecular Surface ...... 55 Setting SolventRadius ... Setting Surface Mapping Partial Surfaces. Coloring by Element ...... 48 Coloring by Group ...... 48 Partial Charge...... Coloring by 48 Anaglyphs...... Red-blue 48 enhancement...... Depth Fading3D 48 Perspective Rendering...... 49 Adding Lone Pairs...... 50 Removing Lone Pairs...... 50 Show/Hide Lone Pairs...... 50 Setting Default Options.. Displaying LabelsAtom by Atom ...... 50 Controlling Separation ...... 52 Solvent-Accessible Surf Solvent-Accessible Connolly Molecular Surf Total Charge Density ...... 58 Total Spin Density ...... 58 MEP ...... 58 Molecular Orbitals ...... 58 Extended Hückel ...... 52 Molecular Su Displaying Displaying Dot Surfaces Dot Displaying Coloring Displays Coloring Displays ...... 47 ColoringBackground the Window ...... 49 Atoms Coloring Individual ...... 49 Lone Electron Pairs ...... 49 Atom Labels Displaying ...... 50 Group Labels Displaying ...... 50 Measurements Displaying ...... 51 Using Stereo Pairs ...... 51 Stereo Enhancement ...... 52 Molecular Surfaces ...... 52 Other Sources ...... Chapter 4 Building and Modifying Models ...... 61 ...... 26 s ...... 23 Hiding Hydrogens...... 26 Hiding Hydrogens...... 26 Adding atoms...... and Labels...... Serial Numbers 27 CleanupStructure 27 ...... Saving the model 28 ...... Spin Density42 ...... Build the first polymer chain37 ...... Build a copy of the chain...... 37 Orient the chains...... 37 Set optimal distances 38 ...... Rotating two dihedrals...... Rotating 34 the chart...... Customizing 35 Rotating models...... Rotating 24 Models...... Examining 25 Saving the File...... 28 Name=Struct...... 29 Stereochemistry 29 ...... 30 Viewing the model...... Building CyclicCompound Structure Display Modes Display Modes Structure ...... 45 Displaying Solid Spheres ...... 46 Displaying Partial Charges Displaying Partial ...... 43 Replacing Atoms ...... 28 Using Labels to Create Models ...... 28 Using Substructures ...... 30 Dual Link Dual Mode ...... 23 Defaults Setting ...... 23 Display Model Setting the ...... 23 Phenol model Building a Unlink Mode ...... 24 vi Structure Displays Structure ...... 45 Tutorial 10: Partial Charges Partial Tutorial 10: ...... 42 Tutorial 8: Viewing Orbitals ...... 39 Tutorial 9: Mapping Surfaces ...... 40 Tutorial 4: Examining Conformations Tutorial 4: Examining Conformations .....31 Driver Dihedral Tutorial 5: The ...... 34 Models Tutorial 6: Overlaying ...... 35 Tutorial 7: Docking Models ...... 37 Tutorial 3: The Text Building Tool Text Building Tool Tutorial 3: The ...... 28 Tutorial 2: Using Bond Tools ...... 24 Using Bond Tools Tutorial 2: Displaying Models ...... 45 Chapter 3

Administrator Setting the Model Building Controls ...... 61 Viewing serial numbers ...... 75 Building with the ChemDraw Panel ...... 62 Reassigning serial numbers ...... 75 Drawing small molecules ...... 62 Changing Stereochemistry ...... 76 Unlink Mode ...... 62 Inversion ...... 76 Name=Struct ...... 62 Reflection ...... 76 Building with Other 2D Programs ...... 62 Refining a Model ...... 77 Building With the Bond Tools ...... 63 Rectifying Atoms ...... 77 Rectification ...... 63 Cleaning Up a Model ...... 77 Adjusting Bond Width ...... 63 Printing and Saving ...... 77 Adjusting all bonds...... 63 Printing ...... 77 Undefined Bonds and Atoms ...... 63 Setting Print Options...... 77 Displaying Delocalized Bonds ...... 64 To Print ...... 78 Removing Bonds and Atoms ...... 64 Saving Models ...... 78 Building With The Text Tool ...... 65 Setting Defaults...... 78 Symbols and Formulae ...... 65 Saving your file...... 78 Changing building types...... 66 Copying and Embedding ...... 78 The Table Editor...... 66 Copying Models...... 78 Specifying Order of Attachment ...... 66 Using Substructures ...... 66 Building with Substructures ...... 67 Chapter 5 Example 1. Building Ethane...... 67 Modifying Models ...... 79 Example 2. Building a Model with a Selecting ...... 79 Substructure and Several Other Elements... Selecting Single Atoms and Bonds ...... 79 67 Deselecting Atoms and Bonds ...... 79 Example 3. Polypeptides ...... 68 Atom Groups ...... 80 Example 4. Other Polymers ...... 69 Using the selection tool...... 80 Replacing an Atom ...... 69 Defining Groups...... 80 Building From Tables ...... 69 Selecting a Group or Fragment...... 80 Examples ...... 70 Selecting by Distance ...... 81 Changing Elements ...... 70 Showing and Hiding Atoms ...... 81 Changing Bond Order ...... 71 Hiding atoms and groups ...... 82 Bonding by Proximity ...... 71 Showing atoms...... 82 Adding Fragments ...... 72 Hydrogens and Lone Pairs...... 82 View Focus ...... 72 Showing All Atoms ...... 82 Setting Measurements ...... 72 Hydrogen Bonds ...... 82 Setting Bond Lengths ...... 73 Moving Atoms or Models ...... 83 Setting Bond Angles ...... 73 The Translate Tool ...... 84 Setting Dihedral Angles ...... 73 Rotating Models ...... 84 Setting close contact Distances ...... 73 X- Y- or Z-Axis Rotations ...... 84 Atom Movement ...... 74 Rotating Fragments ...... 85 Setting Constraints ...... 74 Trackball Tool ...... 85 Setting Charges ...... 74 Internal Rotations ...... 85 Displaying charges ...... 75 Using the Rotation Dial ...... 85 Serial Numbers ...... 75 Rotating Around a Bond ...... 86

Chem & Bio Office 2008: Chem & Bio 3D, ChemScript, and ChemFinder & BioViz vii User Guide ...... 117 ...... 103 ...... hane ...... 112 Dynamics Settings...... Dynamics 116 Job Type Settings ...... Saving a Job ...... 118 Starting the Calculation...... 118 Copying to other applicationsCopying ...... 105 SMILES and InChI™...... 105 Embedding Models ...... 105 Background Effects and Images...... 107 Dihedral angles...... 112 Using constraint values ...... 113 Example: Cyclohexane...... 114 DisplayingAtom MMFF94 Types...... 109 Calculating potential energy...... 110 Minimizing model energy ...... 110 Multiple Calculations ...... 112 Viewing Structure Viewing Structure Properties ...... 103 Addingto your Model.... Nesting ObjectsNesting ...... 102 Repeating a Computation ...... 121 MM2 ...... 109 MMFF94 ...... 109 Energy Minimization ...... 110 Example: Minimizing Et Viewing Structures Structures Viewing ...... 102 drag and drop Model Explorer ...... 103 Moving Objects Objects Moving ...... 102 Modes Display ...... 102 fast overlay ...... 103 About Atom Types Types About Atom ...... 109 Force Fields ...... 109 Molecular Dynamics ...... 116 Compute Properties ...... 118 Showing Used Parameters ...... 120 Defining Atom Types ...... 121 Structure Browser Structure ...... 102 Using the Clipboard ...... 105 Chapter 8 Force Field Calculations ...... 109 Chapter 7 Exporting Models ...... 105 .....101 ...... 102 ...... her Atoms ...... 90 ...... Non-Bonded Distances94 ...... Rotating Around Around a SpecificRotating Axis...... 86 a Angle...... Dihedral Rotating 86 Fragments 100 ...... Chains and groups 100 ...... Bonds...... 100 Solvents 100 ...... Backbone 100 ...... 100 Atoms...... Object Properties 101 ...... Atom Property Table Features...... 96 Z-Matrix Coordinates97 ...... Coordinates...... Cartesian 97 Non-Bonded Distances95 ...... Removing Measurements95 ...... Creating Groups...... 101 Adding to Groups 101 ...... Deleting Groups...... 101 Coloring Groups ...... Resetting Defaults...... 102 Resetting Defaults...... Aligning to an Axis Aligning to ...... 87 a Plane Aligning to ...... 87 Model Explorer Objects ...... 100 Managing Objects ...... 101 Groups ...... Atom Properties Atom Properties ...... 96 Displaying the Coordinates Tables ...... 97 Editing Measurements Editing Measurements ...... 94 Optimal Measurements ...... 95 Positioning by Three Ot Centering a Centering Selection ...... 88 The Zoom Tool ...... 89 Scaling a Model ...... 89 viii Comparing Models by Overlay Comparing Models ...... 97 Model Explorer ...... 99 Deviation from Plane Deviation from Plane ...... 95 The Measurement Table The Measurement Table ...... 94 The Z-matrix ...... 89 Popup Information ...... 93 Resizing Models Resizing ...... 88 Chapter 6 Viewing Models ...... 93

Administrator Chapter 9 Molecular Surfaces ...... 139 Gaussian ...... 123 Polarizability...... 139 COSMO Solvation in Water ...... 139 The Gaussian Interface ...... 123 Hyperfine Coupling Constants...... 139 Predicting Spectra ...... 123 Spin Density...... 140 Viewing Spectra ...... 123 Example 1: Dipole Moment...... 141 Multi-step Jobs ...... 124 Example 2: Cation Stability...... 141 Partial Optimizations ...... 124 Example 3: Charge Distribution ...... 142 Input Template ...... 125 Example 4: The Dipole Moment of m- Advanced Mode ...... 125 Nitrotoluene ...... 143 Support for DFT Methods ...... 125 Example 5: Phase Stability ...... 144 Minimizing Energy ...... 126 Example 6: Hyperfine Coupling Constants Other Options ...... 127 145 Computing Properties ...... 128 Example 7: UHF Spin Density ...... 146 Job Description File Formats ...... 128 Example 8: RHF Spin Density...... 146 JDT Format ...... 128 MOPAC Files ...... 147 JDF Format...... 128 Using the *.out file ...... 147 Creating an Input File ...... 128 Creating an Input File ...... 147 Running an Input File ...... 128 Running Input Files ...... 148 Running a Gaussian Job ...... 128 Running MOPAC Jobs ...... 148 Repeating a Gaussian Job ...... 129 Repeating MOPAC Jobs ...... 148 Creating Structures From ARC Files ...... 149 Chapter 10 MOPAC Calculations ...... 131 Chapter 11 Minimizing Energy ...... 131 Jaguar ...... 151 Notes...... 132 Overview ...... 151 Optimizing Geometry ...... 133 Minimizing Energy ...... 151 TS ...... 133 Optimize to Transition State ...... 152 BFGS...... 133 Predicting Spectra ...... 152 LBFGS ...... 133 Computing Properties ...... 152 Adding Keywords ...... 133 Advanced Mode ...... 152 Optimize to Transition State ...... 134 Locating the Eclipsed Transition State of Ethane...... 135 Chapter 12 Computing Properties ...... 136 GAMESS Computations ...... 153 MOPAC Properties ...... 136 GAMESS Overview ...... 153 Heat of Formation, DHf ...... 136 Gradient Norm...... 137 Minimizing Energy ...... 153 Dipole Moment ...... 137 The Job & Theory Tab ...... 153 Charges...... 137 The General Tab ...... 154 Mulliken Charges ...... 137 Specifying Properties to Compute ...... 154 Electrostatic Potential...... 138 Specifying the General Settings ...... 154 Wang-Ford Charges ...... 138 Saving Customized Job Descriptions .... 155 Electrostatic Potential...... 138 Running a GAMESS Job ...... 155

Chem & Bio Office 2008: Chem & Bio 3D, ChemScript, and ChemFinder & BioViz ix User Guide ...... 197 ...... Parameter Table Fields...... 202 Quality...... 202 Reference...... 202 Alchemy ...... 196 Cartesian Coordinates ...... 196 Connection Table ...... 196 Gaussian Input...... 197 Gaussian Checkpoint...... Gaussian Cube...... 197 CoordinatesInternal ...... 197 MacroModel Files ...... 198 Maestro Files...... 198 DesignMolecular Limited MolFile...... 198 MSI ChemNote ...... 198 MOPAC Files...... 198 MOPAC Graph Files...... 200 Files...... Protein Data Bank 200 (RDL) ROSDAL Files ...... 200 Molecular Data (SMD) Standard ...... 200 SYBYL Files...... 200 JDF Files ...... 200 JDT Files ...... 200 Atom Type Numbers ...... 202 MSI MolFile MSI ...... 178 MOPAC ...... 182 Files Bank Protein Data ...... 183 ROSDAL ...... 186 SMD ...... 186 File SYBYL MOL ...... 188 File SYBYL MOL2 ...... 190 Publishing Formats Publishing Formats ...... 193 Export Formats ...... 196 Job Description File Formats ...... 200 Using Parameter Tables Using Parameter ...... 201 Parameters Estimating ...... 202 Parameters Creating ...... 202 The Elements ...... 203 Types Building ...... 203 Substructures ...... 205 Export File Formats Export File ...... 193 Appendix F Parameter Tables ...... 201 tics ...... 163 Standard Selection 160 ...... Radial Selection...... 160 FORTRAN Formats 171 ...... Name ...... 167 Description ...... 167 Alchemy File ...... 167 Coordinate Files Cartesian ...... 169 Data Bank Files Cambridge Crystal ...... 171 File Internal Coordinates ...... 172 MacroModel ...... 174 MDL MolFile ...... 175 Building Type Characteris Relationships Stereochemical ...... 165 Labels ...... 166 Zoom and Translate ...... 160 Attachment point rules Attachment ...... 157 Angles and measurements ...... 157 Repeating a GAMESS Job Job a GAMESS Repeating ...... 155 x File Format Examples File ...... 167 Editing File Format Atom Types Atom Format Editing File ...... 167 Defining building types Defining building ...... 164 Assigning building Types ...... 163 Assigning building Types Selection ...... 160 Defining Substructures Substructures Defining ...... 157 Appendix E File Formats ...... 167 Appendix D 2D to 3D Conversion ...... 165 Appendix C Building Types ...... 163 Appendix B keyboard modifiers ...... 159 Appendix A Appendix ...... 157Substructures

Administrator References ...... 206 Molecular Dynamics Formulas...... 230 Bond Stretching Parameters ...... 206 Methods Available in CS MOPAC ...... 230 Record Order ...... 207 RHF...... 230 Angle Bending Parameters ...... 207 UHF...... 231 Record Order ...... 208 Configuration Interaction...... 231 Pi Bonds ...... 209 Approximate Hamiltonians in MOPAC 231 Electronegativity Adjustments ...... 209 Choosing a Hamiltonian ...... 232 MM2 Constants ...... 209 MNDO Applicability and Limitations. 232 MM2 Atom Type Parameters ...... 211 PM3 Applicability and Limitations ..... 233 Text type number ...... 211 Torsional Parameters ...... 212 Appendix H Record Order ...... 214 MM2 ...... 235 Out-of-Plane Bending ...... 214 MM2 Parameters ...... 235 van der Waals Interactions ...... 215 Other Parameters ...... 235 Viewing Parameters ...... 235 Appendix G Editing Parameters ...... 235 The MM2 Force Field ...... 236 Computation Concepts ...... 217 Allinger’s Force Field ...... 236 Methods Overview ...... 217 Using Computational Methods ...... 218 Choosing the Best Method ...... 218 Appendix I Molecular Mechanics Theory ...... 223 MOPAC ...... 239 The Force-Field ...... 223 MOPAC Background ...... 239 MM2 ...... 224 Potential Energy Functions ...... 239 Bond Stretching Energy ...... 224 Adding Parameters to MOPAC ...... 240 Angle Bending Energy ...... 225 Using Keywords ...... 240 Torsion Energy...... 226 Automatic Keywords ...... 240 Non-Bonded Energy...... 226 Additional Keywords ...... 241 van der Waals Energy ...... 226 Specifying the Electronic Configuration 241 Cutoff Parameters for van der Waals Interactions ...... 227 Even-Electron Systems ...... 243 Electrostatic Energy ...... 227 Odd-Electron Systems ...... 244 dipole/dipole contribution ...... 227 Sparkles ...... 244 dipole/charge contribution...... 227 Cutoff Parameters for Electrostatic Appendix J Interactions ...... 228 Technical Support ...... 247 OOP Bending ...... 228 Pi Bonds and Atoms with Pi Bonds ..... 228 Serial Numbers ...... 247 Stretch-Bend Cross Terms ...... 229 Troubleshooting ...... 247 User-Imposed Constraints ...... 229 Performance ...... 247 Molecular Dynamics Simulation ...... 229 Applications and Drivers ...... 248

Chem & Bio Office 2008: Chem & Bio 3D, ChemScript, and ChemFinder & BioViz xi User Guide ...... 267 ...... quirements ...... 258quirements option ...... 267 updates ...... 267 ...... Special formats...... Special 257 Main toolbar ...... 265 Form toolbar...... 265 Search toolbar...... 265 Record toolbar...... 265 Text format toolbar...... 266 barThe status ...... 266 Sample databases ...... 271 Style buttontextboxes and frame for ...... 266 Read-only structure box Automatic frame label ...... 267Themes Resizable dialog boxes ...... 267 UI improvements in ChemFinder 11.0 10 267 replace Find and ... The database model ...... 268 and databases forms Understanding ...... 269 Quick reference card Quick reference ...... 257 Help system ...... 258 Microsoft® Windows® re Site license network installation instructions . 258 pages CambridgeSoft web ...... 258 The toolbars ChemFinder 11.0 ...... 265 UI improvements in ChemFinder 11.0 UI improvements .. 266 version of ChemFinder earlier For users of 11.0 ...... 267 ChemFinder 11.0 Opening ...... 268 databases with 11.0 ChemFinder Using 268 ...... Overview 271 Additional information information Additional ...... 257 requirementsInstallation and system .... 258 259 ...... Overview 261 ChemFinder 11.0 UI The ...... 261 Chapter 14 ChemFinder 11.0 Tutorials ...... 271 Chapter 13 11.0 User Interface The ChemFinder .... 261 itro group), write an file, write a list of file, write a ripping ...... 252 file and scaffold, align Conventions ...... 257 Enhancements ...... 255 Enhancements ...... 256 SD file ...... 252 st Example 8: Basic salt Installing ChemScriptand Python ...... 250 Developing Scripts ...... 250 Interactive Mode ...... 251 perform files, list of Example 1: Read a cleanup,liststructure of files write a ...... 251 Example 2: Read a files, write an of list SD file 251 SD Example 3: Read an CDXML files ...... 251 file, filter based on Example 4: Read an SD substructure, write two SD files ...... 252 for SD files, check Example 5: Read two duplicates using canonical codes, write a single SD file ...... 252 Example 6: Read an SD scaffold, write an SD file ...... 252 file, perform a Example 7: Read an SD (n reaction transformation ChemScript Functionality ChemScript ...... 249 About Python ...... 250 xii ChemFinder 11.0/Oracle enhancements 257 this user’s guide About ...... 257 About ChemFinder 11.0® ...... 255 About BioViz ...... 255 new in ChemFinder What’s 11.0? ...... 255 new in BioViz What’s 11? ...... 256 ChemScript Examples ChemScript Examples ...... 251 Introduction ...... 249 Introduction ChemScript Learning ...... 250 Getting Started ...... 250 Section III ChemFinder & BioViz ChemScript SectionII

Administrator Tutorial 1: Creating forms ...... 271 Opening a secured MS Access database .. 299 Creating data boxes ...... 271 Creating a database ...... 299 Editing data boxes ...... 273 Creating forms automatically ...... 299 Deleting data boxes ...... 274 Saving a form ...... 301 Creating and saving a form ...... 275 Creating forms manually ...... 301 Tutorial 2: Opening a database ...... 275 Creating a new form ...... 301 Connecting a database to a form ...... 275 Using the form tools ...... 301 Assigning fields to data boxes ...... 276 Using the grid ...... 302 Tutorial 3: Creating your own database .277 Creating boxes ...... 302 Adding records ...... 278 Creating frames ...... 302 Tutorial 4: Searching a database ...... 279 Creating boxes with frames ...... 303 Opening the demo database ...... 280 Automatic labels ...... 303 Text searching ...... 281 Non-data boxes ...... 303 Formula searching ...... 281 Adding plain text...... 304 Name searching ...... 283 Adding pictures...... 304 Numerical searching ...... 283 Adding a checkbox ...... 305 Substructure searching ...... 284 Adding a button...... 305 Combined searching ...... 285 Adding a subform ...... 305 Tutorial 5: Reaction queries ...... 285 Adding a profile ...... 305 Opening a specific database ...... 285 Adding a control ...... 305 Searching for reactants ...... 286 Creating and editing tabs ...... 305 Searching for products ...... 286 Creating forms with the database tree ... 306 Searching by reaction type ...... 287 Setting box properties ...... 307 Search over list ...... 287 Setting data box styles ...... 307 Tutorial 6:BioViz quickstart ...... 288 Viewing structures ...... 308 Creating a BioViz chart ...... 288 Viewing structures in Chem3D format 308 Single variable plots ...... 288 Setting fixed and live data ...... 309 Histogram plots ...... 289 Adding a data box menu ...... 310 Two-variable plots...... 290 Adding a scroll bars ...... 311 Working with plots ...... 290 Hiding data boxes ...... 311 Filters ...... 291 Customizing text ...... 311 Autoscale...... 291 Customizing fonts ...... 312 Zoom ...... 291 Customizing numbers ...... 312 Statistical analysis ...... 292 Setting color ...... 313 Tutorial 7: Working with subforms ...... 294 Editing forms ...... 314 Creating a subform ...... 294 Selecting objects on a form ...... 314 Moving objects ...... 314 Resizing objects ...... 315 Chapter 15 Deleting objects ...... 315 Creating and Editing Forms ...... 297 Reversing and restoring changes ...... 315 Overview ...... 297 Ordering objects ...... 315 Selecting a database ...... 297 Aligning and distributing objects ...... 316 Opening an existing chemical database ....297 Changing the layout of an existing form .. 317 Selecting the data to display ...... 298 Securing forms ...... 317

Chem & Bio Office 2008: Chem & Bio 3D, ChemScript, and ChemFinder & BioViz xiii User Guide ...... 353 ...... 354 ...... 341 ChemDraw ...... Chem3D ...... se scheme ...... 343 Combined searching example:Combined searching ...... 355 Working with structuresusing 340 Viewing models using Normal searches ...... 348 Exact searches ...... 348 Similarity searches ...... 349 Substructure searches ...... 349 Full structure searches...... 350 Fragment searches...... 350 3D properties...... 351 Alternative groups...... 351 group...... Defining an alternative 352 Undoing changes...... 342 Redoing changes ...... 342 Search types types Search ...... 348 Structure modes ...... 349 Tautomeric searches ...... 350 ...... 351Stereochemistry with R-groups Searching ...... 351 Reaction centers ...... Sorting in languages other than English English than other languages in Sorting ...343 database Resetting the ...... 343 Styled text Styled text ...... 341 Deleting data ...... 342 Atom-to-atom mapping ...... 354 for reactants Searching Searching for products for products Searching ...... 355 for intermediates Searching ...... 355 Reaction searches ...... 353 Combined searches ...... 355 Sorting data Sorting data ...... 342 databa Changing the ...... Overview 345 Text searches ...... 345 Numeric searches ...... 346 Molecular formula searches ...... 346 Date searches ...... 347 Find list ...... 347 Structure searches ...... 348 Chapter 18 Database Queries ...... 345 .....323 ...... 323 ...... 324 ...... 324 ...... es ...... 333 ...... Attaching files from a file-based database from files Attaching .. 330 file-based a non from files Attaching database 330 ...... R-group tables...... 326 R-group tables...... R-Group plots 328 ...... Editing structures ...... 339 Clearing the form ...... 337 Adding new data ...... 337 data Committing the new ...... 338 Duplicating records ...... 338 Undoing data entry ...... 339 Multi-user access Multi-user access ...... Creating tables ...... 329 Deleting tables ...... 329 Attaching tables from other applications ..330 Creating fields ...... 331 Deleting fields ...... 333 Adding multiple structur Read-only access ... The data table ...... 325 Addingstructures to non-chemical databases . 334 Backing up databases ...... 334 Moving databases ...... 334 Setting security options options security Setting ...... 317 security Disabling ...... 321 security Overriding ...... 321 Secured access Secured access ...... xiv Editing data ...... 339 Entering data into a database Entering data into ...... 337 Creating a portal database portal a Creating ...... 335 Creating a database ...... 328 a Creating Browsing databases Browsing databases ... Overview ...... 323 Overview Opening databases ...... 323 Chapter 17 Working with Data ...... 337 Chapter 16 Chapter with Databases Working ...... 323

Administrator SQL searches ...... 355 Importing text files ...... 377 Query procedures ...... 356 Exporting data files ...... 378 Setting search type preferences ...... 356 Saving structures ...... 379 Setting search details preferences ...... 357 Using copy-paste with structures...... 379 Tuning ...... 358 Exporting an ASCII file ...... 380 Setting stereochemical search preferences.. Exporting a Word file ...... 380 358 Export to SDFile ...... 381 Entering query mode ...... 359 Printing ...... 381 Entering and submitting a query ...... 359 Stopping a search ...... 360 Refining a search ...... 360 Chapter 20 Entering a structural query ...... 360 Relational Data and Subforms ...... 383 Using the current molecule as a query . 361 Overview ...... 383 Finding the current molecule...... 361 Accessing relational data using subforms ... Entering a reaction query ...... 361 383 Special structure searches ...... 362 Creating a subform ...... 383 Managing queries ...... 364 Subform changes for users of version 8.0 and The Queries context menu ...... 365 earlier ...... 383 Domains ...... 366 Creating a subform manually ...... 384 Saving and restoring lists ...... 366 Subform generator ...... 385 Saving a hit list...... 367 Changing the layout of an existing subform .. Restoring a hit list ...... 367 386 Search examples ...... 368 Working with subforms ...... 386 Working with multiple hit lists ...... 368 Searching a subform ...... 387 Using atom lists ...... 369 Viewing subform data in a table ...... 387 Atom types and bond types ...... 369 Subform plots ...... 387 Searching fullerenes ...... 369 Using scripts in subforms ...... 388 Searching link nodes and multivalent Rs (MVRs) ...... 369 Searching more than one substructure ...... 370 Chapter 21 Compound Profiles ...... 389 Chapter 19 Creating a compound profile ...... 389 Editing a compound profile ...... 390 Importing and Exporting Data ...... 373 Display preferences ...... 391 Overview ...... 373 Search/sort ...... 392 Supported file formats ...... 373 Example: ...... 392 Importing data ...... 373 Customizing ...... 393 Importing structures ...... 373 Importing structure data and reaction data files 375 Chapter 22 Using log files ...... 376 Visualizing Data With BioViz ...... 395 Importing from a specified location ..... 376 Changes in version 11 ...... 395 Reading a structure ...... 377 User-customizable styles ...... 395 Drag and drop...... 377 Point shapes ...... 395

Chem & Bio Office 2008: Chem & Bio 3D, ChemScript, and ChemFinder & BioViz xv User Guide ...... 415 ...... 423 ...... lists ...... 419 ...... 416 a single tab ...... 421 rformance ...... 421 ...... s ...... 420 hitlists ...... 417 Settingpassword”. “save Query Query control display...... 420 Cancelling the domain...... 420 dataset...... Exporting the 420 file cfxml Importing the ...... 421 Structure display...... 423 Using keyboard shortcuts...... 423 Scaling structures ...... 424 Framing pictures...... 424 Grid spacing ...... 424 Changing the query name...... Changing 417 the display color...... Changing 417 Child lists...... 418 child multiple Creating Merging lists with drag-and-drop...... 419 Performing searches in BioSAR in BioSAR searches Performing ...... 415 Exporting the data to ChemFinderform ...415 ChemFinder filetypes: bsbxml cfx and ....415 Creating a domain Creating ...... 420 Access database rules ...... 420 Creating a local copy of a database ...... 420 Excel spreadsheet an Exporting to ...... 421 Tips for optimizingpe Use domain-linked forms ...... 421 Minimize child tables on Removethat plots you using are not ...... 422 preferences Display ...... 423 Color preferences ...... 424 Sorting by main form Sorting by fields ...... 416 fields subform by Sorting the Viewing query list ...... 417 operations list Query ...... 417 Saving query lists ...... 419 Creating an mdb database Creating ...... 420 ...... Overview 423 Setting preferences ... Subforms and autolinks Subforms ...... 415 sort Multiple ...... 416 Working with query Working with domain Chapter 25 Customizing ChemFinder 11.0 ...... 423 s ...... 396 Axes 395 ...... Legend395 ...... colorBackground 396 ...... Other changes 396 ...... Filter slider adjustment 403 ...... Starting the BioSAR browser Starting the ...... 415 Sortingsubform by value aggregate ...... 410 Synchronization of plots ...... 404 Histograms ...... 398 Plot options ...... 398 Filtering ...... 402 Removal points of empty ...... 396 Selection and mouse-over Details window ...... 396 xvi Getting started ...... 415 Handling lists ...... 410 preferences Setting Oracle ...... 411 data adding Updating and ...... 411 Loading ...... 412 Indexing ...... 412 CAL ...... 414 Overview ...... 407 new in ChemFinder What’s 11.0? ...... 407 Setup ...... 407 Opening an Oracle database ...... 408 Searching ...... 409 Sorting ...... 409 Plotting queries ...... 403 Changing the display ...... 405 Creating a plot a Creating ...... 397 Statistical analysis ...... 401 filtering .... and Cleaning up the plot–sorting 402 Changes in version 10 Changes version in ...... 396 Using ChemFinder 11.0 with BioSAR ... 415 Chapter 24 Chapter 23 ChemFinder/Oracle ...... 407

Administrator Structural query matching ...... 424 Saving data sources as dsd files ...... 444 General preferences ...... 425 Saving lists of directory paths as dsd files 444 Structure registration options ...... 425 Searching DSD files ...... 445 ChemFinder 11.0 opening options ...... 425 Sending a file to another application ..... 445 Setting the recent file list size ...... 425 Refining your search ...... 446 Changing options with the view menu .....426 Using the search tools ...... 447 Customizing the favorites tree ...... 426 Refining your query with the search options . Customizing toolbars ...... 427 447 Using the periodic table ...... 428 Changing ChemFinder/Office settings .. 449 Embedding ActiveX controls ...... 429 Customizing the ChemFinder/Office window Customizing controls ...... 429 449 Scripting, Part I: CAL ...... 429 Changing the ChemFinder/Office preferences Getting CAL help ...... 430 450 Creating a script ...... 430 Debugging a script ...... 431 Trigger scripts ...... 431 Appendix A Scripting Part II: Python™ ...... 432 Structural Query Features ...... 451 About Python ...... 432 Overview ...... 451 Creating a script ...... 433 General properties ...... 451 The script editor ...... 433 Atoms ...... 451 Interactive mode...... 434 Bonds ...... 451 The output window...... 434 Substituents ...... 452 Communicating with other applications 435 Charges and radicals ...... 452 Using scripts ...... 435 Isotopes ...... 453 Using Visual Basic ...... 436 Stereochemistry ...... 453 Using Microsoft Access with ChemFinder Relative tetrahedral stereochemistry.... 454 11.0 ...... 437 MDL file formats ...... 454 Normalization ...... 455 Changing the scope of a search ...... 456 Chapter 26 Atom properties ...... 456 ChemFinder/Office ...... 439 Special atom types ...... 456 Overview ...... 439 Atom lists ...... 456 The ChemFinder/Office user interface (UI) . Atom not-lists ...... 456 439 Substituents: exactly ...... 456 Selecting files to search ...... 440 Substituents: up to ...... 457 Selecting files from the file menu ...... 440 Substituents: free sites ...... 457 Selecting files with the look in tab ...... 440 Implicit hydrogens ...... 458 Searching by chemical structure ...... 441 Unsaturation ...... 458 Searching by multiple properties ...... 442 Bond properties ...... 458 Browsing search results ...... 443 Special bond types ...... 458 Saving files or data sources ...... 444 Topology...... 459 Reaction center ...... 459 Saving search results as sdf files ...... 444

Chem & Bio Office 2008: Chem & Bio 3D, ChemScript, and ChemFinder & BioViz xvii User Guide New in ChemFinder 11.0 ChemFinder 11.0 ...... 469New in Pre-setup procedures Pre-setup ...... 481 Fast-move caching scheme ...... 481 Configuration via CF_SETTINGS table 482 Searching ...... 483 Overview ...... Overview 469 CAL help ...... 469 Menu commands ...... 469 commands Box creation ...... 470 commands Box manipulation ...... 471 Program execution commands ...... 472 commands General ...... 473 File commands ...... 474 Database commands ...... 474 Variable commands ...... 475 Environment variables ...... 477 Script-only commands ...... 477 Appendix F CS Oracle Cartridge ...... 481 Index ...... 485 Appendix E Appendix Commands CAL ...... 469 ActiveX ChemDraw ilarity ...... 467 templates ...... 461templates ity ...... 468 or the or ChemDraw Reaction template basics Reaction template ...... 461 Using control ...... 462 a ChemFinderUsing 11.0 database: ...... 462 xviii Substructure similar Overview ...... 467 Complete structure sim Overview ...... 465 Rules ...... 465 ...... 465 Examples CombiChem overview ...... 461 overview CombiChem with reaction Working ...... 461 template a Entering Similarity Rules ...... 467 Appendix D Appendix C Rules Formula Input ...... 465 Appendix B Appendix Using with ChemFinder/Office Com- biChem ...... 461

Administrator Section I: Chem & Bio3D 11.0

Chem & Bio 3D 11.0 enables you to create color plug-in. Contact CambridgeSoft Sales or your local models of chemical and biochemical compounds. reseller for details. Once you have a model, you can calculate a variety of molecular properties—electrostatic potentials, About Gaussian bond energies, and spectrum prediction, and more. Gaussian is a cluster of programs that are available It combines powerful building, analysis, and com- for you to perform semi-empirical and ab initio putational tools with intuitive menus and a power- molecular orbital (MO) calculations. ful scripting interface.

About CS MOPAC NOTE: Gaussian is available only for ChemBio3D 11.0 Ultra and may be purchased separately. See www.Cam- CS MOPAC is an implementation of the well bridgeSoft.com for more information. known semi-empirical modeling application MOPAC, which takes advantage of the easy-to-use interface of Chem & Bio 3D 11.0. CS MOPAC When Gaussian is installed (if it is not, the Gauss- currently supports MOPAC 2002. ian menu option is gray), Chem & Bio 3D 11.0 There are two CS MOPAC options available with communicates with it and serves as a graphical Chem & Bio 3D 11.0: front end for Gaussian’s text-based input and output. Chem & Bio 3D 11.0 is compatible with •MOPAC Ultra Gaussian 03 for Windows and requires the 32-bit •MOPAC Pro version. MOPAC Ultra is the full MOPAC implementation, and is available only as an optional plug-in. CS About Jaguar MOPAC Ultra provides support for previously SCHRÖDINGER® Jaguar is a high-performance unavailable features such as MOZYME and PM5 ab initio package for both gas and solution phase methods. simulations, with particular strength in treating With MOPAC Pro, you can perform simple and metal containing systems. It is a practical quantum advanced energy minimizations, optimize to transi- mechanical tool for solving real-world problems. tion states, and compute various properties. CS The new Chem & Bio 3D interface is the only MOPAC Pro supports MOPAC sparkles, has an Windows platform GUI for Jaguar. improved user interface, and provides faster calculations. See “MOPAC Calculations” on page 131 NOTE: Jaguar is available only for ChemBio3D 11.0 for more information on using CS MOPAC. Ultra. CS MOPAC is included in some versions of Chem & Bio 3D 11.0 or may be purchased as an optional

Chem & Bio 3D 11.0 1 User Guide Introduction 2 Chapter 1

Administrator New in Chem & Bio 3D 11.0

The Chem & Bio 3D 11.0 family of products Features includes Chem3D Pro 11.0, Bio3D Ultra 11.0, and ChemBio3D Ultra 11.0. Each of these powerful Chem & Bio 3D 11.0 introduces a variety of and versatile applications is uniquely designed to improvements and new features not found in ear- meet the demanding requirements of chemical and lier versions. The new features are briefly described biochemical modeling. Whether you are studying below. You can find more information on these the tertiary structure of a protein or the thermal and other features throughout the manual and properties of new polymer, one of these products online Help. will likely meet your needs. Atom Properties. New in version 11.0 is the Atom Property table. This table lists calculations Chem3D Pro 11.0 you perform on your model and can be saved with This latest version of Chem & Bio 3D 11.0 has the model. Also, in earlier versions, there were just numerous new features that were never available in a few properties available by which you could earlier versions. Chem3D Pro 11.0 is specifically color-code a model. With version 11.0, you can designed for studying small molecules and their select virtually any property that is based on a cal- properties such as quantum mechanics, reactivity, culated result, a Chem 3D file, Maestro file, or a and thermal characteristics, just to name a few. custom property that you define yourself. Bio3D Ultra 11.0 Formal and delocalized charges. Chem & Bio 3D 11.0 displays the formal charge that appear in With Chem & Bio Office 2008, CambridgeSoft the ChemDraw panel. Then, using MM2 format, it proudly introduces Bio3D Ultra 11.0. Here you calculates and displays the delocalized charge for will find a host of new features that cater to users each charged atom. Hover the mouse over an atom who specialize in the biology and biochemistry sci- to view. ences. For instance, use Bio3D to identify protein binding sites, analyze RNA fragments, or view vir- Structure Browser Window. This feature lets you tually any complex biology models. quickly scan through a list of small molecules (and their properties) that have been saved to a file and ChemBio3D Ultra 11.0 view the models on screen. You can then select any ChemBio3D Ultra 11.0 includes all the features of the models you may want from the list and drag found in Bio3D Ultra 11.0 and Chem3D Pro 11.0. them into the Model window. The structure CambridgeSoft also makes available Jaguar and browser is available in ChemBio3D Ultra 11.0 and Gaussian for performing advanced quantum Bio3D Ultra 11.0. For information on the Struc- mechanics calculations. ture Browser and how to use it, see “Structure Browser” on page 102 of the Chem & BioOffice 2008 User Guide. NOTE: Gaussian is available only for ChemBio3D 11.0 Ultra and may be purchased separately. See www.Cam- Model Explorer Improvements. The Chem & bridgeSoft.com for more information. Bio 3D 11.0 Model Explorer offers several enhancements. You can now move structures and

Chem & Bio3D 11.0 3 User Guide fragments from one place to another in the win- model. However, in Chem & Bio 3D 11.0, you can dow by simply dragging them where ever you want. you add them or remove them altogether. You can also select which ones are visible and even Kekule/delocalized bonds. You can now toggle color-code them based on properties that you aromatic models between their Kekule and delocal- choose. For more on the Model Explorer, see ized structures. “Moving Objects” on page 102 of the Chem & BioOffice 2008 User Guide. Adjustable bond sizes. In earlier versions of Chem & Bio 3D, the bond sizes you set in the MMFF94 Force Field method. In addi- Model Settings dialog box applied to the entire tion to MM2, ChemBio3D 11.0 includes the model. Although this feature is still available in ver- MMFF94 force field method for performing calcu- sion 11.0, you can also customize the size of indi- lations. MMFF94 has been specifically developed vidual bonds, helping you to create your models to to perform energy calculations on protein and look just the way you want. other biological structures. The MMFF94 force field method is available in ChemBio3D Ultra 11.0 ChemDraw synchronization options. A new and Bio3D Ultra 11.0. feature, the Preview Link, lets you select a model fragment in the Chem 3D Panel so that only that Building Types. Chem & Bio 3D 11.0 introduces fragment is displayed in the ChemDraw panel. This “Building Types” for defining the structure of becomes quite useful when you want to view models. Each atom has an assigned building type sequences in polymers and other large molecules. that defines its contribution to the structure of One nice way to use this feature is to open a large your model. The building type defines the geome- molecule and select various fragments listed in the try, bond angles, and bond lengths. Model Explorer. The Chem 3D panel shows where In earlier versions of Chem & Bio 3D, MM2 atom in your model the fragment is while the Chem- types helped defined model structures and were Draw panel simultaneously shows its structure. also used to predict molecular properties. In ver- Store Calculation Output. Chem & Bio 3D 11.0 sion 11.0, MM2 (and now MMFF94 as well) is used lets you copy calculation comments and results only for performing energy calculations and do not from the Output window to the Comments win- define the model structure when you build a dow. This means that you can now save all the model. information with your model. Maestro file format support. Chem & Bio 3D 11.0 supports the Maestro file format for Support for Office 2007 Schrödinger calculations. Chem & Bio 3D 11.0 supports Microsoft Office Add/Remove lone pairs. In earlier versions of 2007. This means you can use the latest software to Chem & Bio 3D, you could only display or hide add a model to your Word document, Excel lone electron pairs in models. This means that, spreadsheet, PowerPoint presentation, or even if they were hidden, they were still part of the FrontPage Web site.

Chem & Bio3D 11.0 4 User Guide Chapter 1: Chem & Bio 3D 11.0 Basics

Getting Around Output and Comments boxes, the Model Explorer, tables, and the ChemDraw Panel. The Status bar The main screen consists of a model window, displays information about the active frame of your menus, toolbars and dialog boxes. It can also model and hidden atoms. include up to three optional panels that display the

Building Toolbar Model Display Toolbar Demo Toolbar Calculation Toolbar ChemDraw Panel tab Title bar

Menu bar Standard Toolbar Active Window Tab

Model Explorer tab

Model Area

Status bar

Figure 1.1Chem & Bio 3D GU. The GUI is shown in Rotation mode with the dynamic Rotation bars showing, the ChemDraw panel open, and the Tables panel set to Auto-Hide.

The Model Window the model, such as calculation results, you can find it in the Output window or the Status bar. The Model window is the work space where you build your model. If there is text information about

Chem & Bio 3D 11.0 5 User Guide X-axis bar, is bar, Show Mouse Rotation tab. Rotate About Bond Rotate About Y-axis GUI Z-axis and select the tab of the Preferences dialog box. dialog tab of the Preferences GUI checkbox on the on checkbox Bond axis File > Preferences Saving Models is window feature of the Model One convenient simply right-click- model by your can save that you can You itsingof the window. name at the top model as the or close print, save, to then choose desired. Box Dialog Preferences style options, includes now customization GUI and Model Explorer display settings, window The VS 2005 (Whidbey) style option options. Changeincludes smart of set- docking toolbars. tings on the Figure 1.2: Rotation bars Rotation 1.2: Figure the The left rotation bar, Zones active only when a bond or dihedral is selected. To only when a bond oractive dihedral is selected. To rotate the image, drag in the main window. freely The cursor changes to a hand freehand rotation mode. are in when you them), go disabling hide the bars (without to To screen only when you screen only when you The workspace where a molec- where a The workspace ular model built, viewed, is or modified, Theanalyzed. ori- the Cartesiangin of axes located at the (0,0,0) is always regard- center of this window, model is the less of how The or scaled. Carte- moved relative not move do sian axes to the window. 10.0 can open Chem & Bio 3D simulta- models multiple The tab selects the neously. window. active 6 Chapter 1 tool . window. anywhere in the model ObjectModel area Description Window Active tab Rotation Bars Rotation view it, the model as to rotate your you want If you to select an way rotation a convenient bars provide axis of rotation.The rotation bars are hidden by default and appear on your are actually using them. model, do the following: rotate a To 1. selecting the Trackball rotation mode by Activate 2. from and drag any of the rotation barsto Click The following table describes the objects in the objects the table describes The following window. Model

Administrator Figure 1.3: GUI Preferences dialog The File Menu In addition to providing other commands, the File menu includes the Chem & Bio 3D Templates, Pref- erences, and Model Settings. Import File. Import MOL2 and SD files into Chem & Bio 3D documents. Model Settings. Set defaults for display modes and colors, model building, atom and ligand display, atom labels and fonts, movie and stereo pair settings, and atom/bond popup label information. Preferences. Set defaults for image export, calculation output path, OpenGL settings and including hydrogens in CDX format files. Sample Files. Open example models. To introduce yourself to Chem & Bio 3D, you may consider taking a look at the sample files. These Menus and Toolbars include a variety of simple and complex models You can select any command or function from representing compounds found in research and either the menus or toolbars. The toolbars contain academia. icons that offer shortcuts to many commonly used The Edit Menu functions. Go to View>Toolbars to activate the toolbars you want. The Edit menu offers a list of fundamental commands that you can apply to your models: Detaching toolbars Copy as. Puts the model on the Clipboard in Depending on the way you work, you may decide ChemDraw format, as a SMILES1 string, or in bit- that the toolbars aren’t always where you want map format. them. To move any toolbar, you can detach it from the top of the screen and drag it to any part of the Copy As ChemDraw Structure. Puts the model GUI. on the Clipboard in CDX format. You may only paste the structure into an application that can To detach a toolbar, click and drag its left-most accept this format, for example Chem & Bio Draw, border onto the Model window. You can then click ChemFinder & BioViz, or Chem & Bio 3D. and drag its title bar to move it anywhere on the screen you want. Copy As SMILES. Puts the model on the Clip- board as a SMILES string. You can paste the structure only into applications that can accept this TIP: Most toolbar commands are duplicated from the format. menus, and are available for your as a convenience. If you only use a command infrequently, you can save clutter by using the menu commands. 1. A text string that represents the structure of a molecule.

Chem & Bio 3D 11.0 7 User Guide ions. It can also create ions. —A toggle—A to switch —Displays or hides the or hides the —Displays —A toggle—A to dis- switch —Displays or hides atom —Displays —A toggle to create a switch —A togglethe enhance to switch —Displays or hides or the model —Displays —A toggle to create a per- switch —A toggle to set the display switch Residue labels appear only when a proteinResiduelabels appear onlystruc- when Show Atom Symbols Atom Show play what each atom is carbon, oxygen, hydro- oxygen, is carbon, atom each what play etc. gen, Serial NumbersShow atom Each the serial number. hide or display it. to identify used number has a unique Residue Labels Show 3D view. acid residues in the names of amino Show Atom Dots Show Themodel. for the is dot surface dot surfaces partialor radius Waals der van on based of the table set in the Atom Display as charges, Settingsbox. dialog Red &Blue for optimal viewing with red-blueglasses to 3D create a stereo effect. Stereo Pairs a model with two displaying by 3D effect slightly different orientat orthogonal front and (simultaneous side) views. The degreeof separation Stereo set on the is View tab of the Settings dialog box. Perspective rendering consistent of the model by spective ofscaling bond and lengths atom sizes by depth. The degree of scaling is controlled by the View” slider on “Field of the Perspective Settingsthe dialog tab of box. Model Display Fading Depth realistic deptheffect, where more distant parts modelthe fade into the background. of The degree the Depth is controlled of fading by on the Model of View” slider “Field Fading tab of thedialog Settings box. Display Model Axes axes. • • • • • • • • • NOTE: ture is displayed in the window. Model —A toggle to switch —A toggle to switch the view, fitting the the view, —A toggle to display switch If you have selected an atom, have If you Puts the model on the Clip- the on the model Puts This submenu provides a variety variety a This provides submenu The View Position submenu pro- submenu TheView Position Preservescoordinates when past- Use the View Focus submenus to set to submenus Use the View Focus Selects the entire model. The application you paste into must recognize you The application the Clears the Model window of all structures. of window Clears the Model 8 Chapter 1 Show Hydrogen Atoms Hydrogen Show Bonds Hydrogen Show mole- bonds between or hide hydrogen display cules. Pairs Lone Show or hide lone pairs of electrons. display or hide hydrogen atoms. or hide hydrogen display • • • of options for you to change the way your model your to change the way options for you of options changeModel Display the None of looks. displayed. is it the model; they only change how the focus. See “View Focus” on page on 72 Focus” “View See the focus. Model Display. The View Menu The View and position to select the view menu View the Use and panels that tables, toolbars, as the as well focus, of the submenu TheDisplay Model are visible. in the all of the commands duplicates View menu toolbar. Model Display View Position. vides optionscentering for and aligning view with an axis. the window, View Focus. board as a bitmap. You paste can the structure only You board as a bitmap. into applications that can accept bitmaps. NOTE: document. tureMicrosoftinto a Word Special. Paste Copy As Picture. As Copy one documentBio 3D model from ing a Chem & to another. Clear. Select All. Fragment. Select that atom belongs. to selects the fragment which format. For example, you cannot paste a ChemDraw struc- cannot paste a ChemDraw you example, format.For

Administrator • View Axes—Displays or hides the view axes. late tool . Use the Move tool to move atoms and fragments. NOTE: When both axes overlap and the Model axes are • Model Display toolbar—Contains tools to displayed, the View axes are not visible. control the display of the model. These tools are duplicated on the View menu. • Background Color—Displays the Back- • Surfaces toolbar—Contains tools to calculate ground color select toolbar. Dark backgrounds and display a molecular surface. Molecular Sur- are best for viewing protein ribbon or cartoon face displays provide information about entire displays. Selecting red-blue will automatically molecules, as opposed to the atom and bond override the background color to display the information provided by Structure displays. optimal black background. Background colors • Calculation toolbar—Performs MM2 minimi- are not used when printing, except for Ribbon zation from a desktop icon. The spinning- displays. When saving a model as a GIF file, the arrow icon shows when any calculation is run- background will be transparent, if you have ning; use the Stop icon to stop a calculation selected that option for Image Export in the before its preset termination. Preferences dialog box. • Status bar—Displays the Status bar, which dis- • Background Effects—Displays how the plays information about the active frame of shade gradient appears. your model. • Color By—Selects the model coloring scheme. • Customize—Displays the Customize dialog See “Coloring Displays” on page 47 for more box. Customizing toolbars is a standard information. Microsoft Windows operation, and is outside the scope of this documentation. Toolbars. Click the name of a toolbar to select it for display. Click again to deselect. You can attach a Model Explorer. Displays a hierarchical tree rep- toolbar to any side of the GUI by dragging it to resentation of the model. Most useful when work- where you want it attached. If you are using a floating with complex molecules such as proteins, the ing toolbar, you can change its shape by dragging Model Explorer gives you highly granular control any of its edges. over the model display. • Standard toolbar—Contains standard file, ChemDraw Panel. Displays the ChemDraw edit, and print tools. The commands are also Panel. Use the ChemDraw Panel to build mole- available on the File and Edit menus. cules quickly and easily with familiar Chem & Bio • Building toolbar—Contains the Select, Trans- Draw tools. You can import, export, modify, or late, Rotate, and Zoom tools in addition to the create small molecules quickly and easily using the model building tools—bonds, text building Chem & Bio Draw ActiveX tools palette. tool, and eraser. These tools are not duplicated Cartesian Table. Displays the Cartesian Coordi- on any menu. This toolbar is divided into nates table. Cartesian Coordinates describe atomic “safe” and “unsafe” tools. The four “safe” position in terms of X-, Y-, and Z-coordinates rela- tools on the left control only the view – they do tive to an arbitrary origin. not affect the model in any way. This includes Z-Matrix Table. Displays the internal coordi- the new “safe” select tool and the trans- nates, or Z-Matrix, table. Internal coordinates are

Chem & Bio 3D 11.0 9 User Guide

and — Actual Actual Optimal Optimal —Displays —Displays —Displays bond —Displays —Resizes and —Resizes —Displays bond —Displays Angle Bending Param- Bending Angle —Resizes and cen- —Resizes Bond Stretching Parameters Stretching Bond Angle Bending Parameters Angle Bending The options in this submenu let The options in this submenu The Model on the Reflect options values come from come values —When three atoms are selected, moves —When three atoms are selected, moves values come from the model and the come values from the right-click menu. from the right-click —Clears the entire Measurement table. If table. Measurement —Clears the entire and other external tables. Center Model on Origin Center Model ters the model in the model window. Center Selection on Origin centers the selected portion of the model in the Model window. or Z-} Axis {X-, Y-, Align Model With them to moves are selected, atoms When two depending of on which Z-axis, or the X-, Y-, choose. you items menu the three or Y-Z} X-Z, {X-Y, With Model Align Plane dependingplane, X-Z, or Y-Z them to the X-Y, choose. items you threethe menu of on which Clear part select clear to of the table, only want you and choose to clear, the portion want you eters Generate All Bond Lengths Bond All Generate The Table. in the Measurement lengths values come from the model and the from the model come values values come from the model and the come from the values values come from the come from values values come from Delete Actual Optimal external table. Bond Angles All Generate The Measurement angles in the Table. other external tables. GenerateDihedral All Angles The Table. angles in the Measurement dihedral • • • • • • • • Reflect Model. reflect the model through a 2-coordinate submenu select, negatingplane that you the third coordinate. will this centers If the model contains any chiral Pro-R posi- changeenantiomer. model the into its Model Position. Model Position. to the win- model relative your and align move you axes. dow New in Chem & Bio 3D mmands populate the Mea- Displays the Measurement the Measurement Displays Displays a list of externalDisplays Displays the Comments box, a the Comments box, Displays Opens the window displaying displaying Opens the window The options below allow you to you The allow options below Displays the Output box, which pro- which the Output box, Displays View the model in full screen display Displays or hides the Status Bar. or hides the Status Displays Provides options to spin the model on the Provides 10 Chapter 1 surement table and control movement of the table and control movement surement model. Measurements. model. your in distances and bond angles measure The Structure Menu The Structure The Structure co menu the most commonly used coordinates for coordinates used commonly the most prepar- for further model ing a computation. Measurement Table. table. The Measurement table displays bond bond The displays Measurement table table. ring clo- and angles, dihedral bond angles, lengths, sures. Atom Property Table. These comments to add comments. place for you it. save file when you the with are stored Dihedral Chart. 11.0, the Atom Property Table displays calculated calculated displays PropertyAtom the 11.0, Table See “Atom model. atom in the properties for each Properties” on page 96 for more information. Tables. Parameters to construct3D uses Bio tables that Chem & mod- results. and display perform computations, els, Output Box. vides information etc. about the model, iterations, with the is not saved The content in the output box model. Comments Box. See computations. MM2 of Dihedral Driver results 5: The on page Dihedral Driver” “Tutorial 34 for more information. Demo. from differ- model your view Thisyou lets Y-axis. it rotates. as ent perspectives Full Screen. with the entire GUI hidden. Press Chem & Bio 3D to close the view. Esc Status Bar.

Administrator tioned atoms will become Pro-S and Pro-S posi- Deviation from Plane. When you select four or tioned atoms will become Pro-R. All dihedral more atoms, this option outputs the RMS devia- angles used to position atoms will also be negated. tion from the plane to the Output window. • Through XY Plane—Reflects the model Add Centroid. Adds a centroid to a selected through the XY plane by negating Z coordi- model or fragment. At least two atoms must be nates. selected. The centroid and “bonds” to the selected • Through XZ Plane—Reflects the model atoms are displayed, and “bond” lengths can be through the XZ plane by negating Y coordi- viewed in the tool tips. To delete a centroid, select nates. it and press the Delete or Backspace key. • Through YZ Plane—Reflects the model through the YZ plane by negating X coordi- NOTE: You cannot add a centroid to a model or fragment nates. when more than 12 atoms are selected. • Invert Through Origin—Reflects the model through the origin, negating all Cartesian coor- Rectify. Fills the open valences for an atom, usu- dinates. ally with hydrogen atoms. This command is only The Set Z-Matrix submenu useful if the default automatic rectification is Set Origin Atom—Sets the selected atom(s) as turned off in the Model Settings dialog box. the origin of the internal coordinates. Up to three Clean Up. Corrects unrealistic bond lengths and atoms may be selected as either the origin atom or bond angles that may occur when building models, an atom positioned relative to the origin atom. See especially when you build strained ring systems. “The Z-matrix” on page 89 for more information. Bond Proximate. If two atoms are close enough Position by Dihedral—Positions an atom relative together to be bonded, this option will provide a to three previously positioned atoms using a bond covalent bond between the two. Go to File>Model distance, a bond angle, and a dihedral angle. For Settings>Model Building tab and use the Bond Proxi- more information on changing the internal coordi- mate Addition slider to specify the maximum dis- nates see “Setting Dihedral Angles” on page 73. tance between atoms for which this feature can be Position by Bond Angles—Positions an atom used. relative to three previously positioned atoms using Lone Pair. Adds and removes lone electron pairs. a bond distance and two bond angles. For more You can also hide or show them after you add information on changing the internal coordinates them. see “Setting Bond Angles” on page 73. Overlay. The Overlay submenu provides all of the Detect Stereochemistry. Scans the model and commands to enable you to compare fragments by lists the stereocenters in the Output box. superimposing one fragment in a model window Invert. Inverts the isomeric form. For example, to over a second fragment. Two types of overlay are invert a model from the cis- form to the trans- possible: quick and minimization. See “fast over- form, select one of the stereo centers and use the lay” on page 103, and “Comparing Models by Invert command. Overlay” on page 97 for information on each overlay type.

Chem & Bio 3D 11.0 11 User Guide the tools see “Building Move tool Single Bond tool Double Bond tool Bond tool Triple Uncoordinated Bond tool Text tool tool Eraser Figure 1.5: The Rotation The Rotation dial 1.5: Figure detailed descriptions of For on page Mod- 63, “Rotating With the Bond Tools” pageModels” on els” on page and 84, “Resizing 88. The Model Display Toolbar The toolbar contains tools Model Display for all of The functions. the Chem & Bio 3D 11.0 display Model type and Backgroundactivate color tools All options. the one of choose thatlet you menus of the remaining tools are toggle switches—click again click to deactivate. once to activate; The rotation dial The rotation to rotate an a model you Dial lets The Rotation the arrow clicking it by Activate specify. you angle and then tool, an axis, select Trackball the under box. in the number type a or drag the dial “Safe” Select tool only) (view tool Translate tool Rotate activator Dial Rotation Zoom tool Use the Dock to command a position Dock Use the frag- New File Open File Save File Copy Cut Paste Undo Redo Print 12 Chapter 1 The Building Toolbar cre-The toolbar Buildingcontains tools to let you ate and manipulatemodels: Thetoolbar Building Figure 1.4: The Standard toolbar Standard 1.4: The Figure The Standard Toolbar The Standard The toolbar Standard contains tools for standard up to 20 steps including of functions, Windows Undo and Redo. Dock. rela- proximity and orientation into a desired ment fragment remains fragment. Each to a second tive rigid computation. during the docking

Administrator Figure 1.6: The Model Display toolbar Figure 1.7: The Surfaces toolbar

Model type Surface

Background Color Solvent radius

Background Effect Display mode

Red-Blue Stereo Color Mapping

Chromatek Stereo Resolution

Perspective

Depth Fading Molecular Orbital selection

Model Axes Isovalues View Axes

Color A Atom labels

Atom numbers Color B Residue label

Full screen mode For more information, see “Molecular Surfaces” on page 52. The Surfaces Toolbar The Demo Toolbar The Surfaces toolbar controls the display of molecular surfaces. In most cases, you will need to per- The Demo toolbar lets you either spin or rock back form either an Extended Hückel, MOPAC, or and forth your model through a range of motion Gaussian calculation before you can display sur- that you specify. faces.

Chem & Bio 3D 11.0 13 User Guide

Draw>3D Replace or When you select a structure select you When (or Draw>3D Add Draw>3D The panel ChemDraw and Model win- The ChemDraw panel and Model window window panel and Model The ChemDraw replace Link Mode Link Draw > 3Dadd Draw>3D Clean up structure Clear Lock 3D>Draw Name=Struct Name=Struct dow are linked so that when you create a structure create a when you so that are linked dow in it also appears the other. in one, Preview Link. the selection part of it) in the Model window, appears inpanel. the ChemDraw Unlink. are notlinked. Use the 3D > Draw icon to drag a model into the drag a model icon to 3D > Draw the Use panel. ChemDraw in the click a model in ChemDraw, create To tool- ChemDraw the panel to activate ChemDraw the Use bar. Linking windows for options three panel includes The ChemDraw to link it you Model with the Window. Link. Dual Figure panel ChemDraw The 1.10: Figure icons to put the model in Chem & Bio 3D. You can You icons to put the model in Chem & Bio 3D. of a com- typing the name also create a model by pound—or a SMILES string—intothe modifying, Name=Struct™ finish When you box. the appropri- clicking add or replace model by your ate icon.

Rock or button. Spin Stop button Stop Stop Stop Amplitude Spin Speed . By default the panel opens Rock Axis select MM2 minimization MM2 minimization 14 Chapter 1 Calculation indicatorstatus View>ChemDraw Panel View>ChemDraw The ChemDraw Panel Chem & Bio 3D 11.0 Panel, With the ChemDraw of it easy your to makes modify drawings create or go to Panel, ChemDraw the activate To models. Figure 1.9:The Calculation toolbar Figure The Calculation Toolbar icon a desktop provides Thetoolbar Calculation for performing MM2 minimization. It also pro- and a calculationindica- vides a Stop button status with all calculations. tor thatwork You can set the speed, amplitude (the range)amplitude can set the speed, and You the model moves. Z) upon which or the axis (X, Y, the clicking either by Stop the demo Figure 1.8: The Demo toolbar 1.8: The Demo Figure on the right side of the screen; but, like the tool- but, like screen; the on the right side of it “float”anywhere. it or attach can have you bars, button a second time or click the timeclick button a second or

Administrator The synchronized windows become a particularly All of the tables have an auto-hide feature to mini- useful feature when you want to examine large mize their display. For more information on Model molecules. Try opening a model that comprises Tables, see “Model Coordinates” on page 20. many fragments. Next, navigate through the vari- Figure 1.11: The Z-Matrix table ous fragments in the Model explorer while the Column Field Name Cell ChemDraw panel and Model window are synchro- Record Heading nized. Each fragment is highlighted in the Model Selector Column Divider window while the ChemDraw panel displays the fragment structure. Draw to 3D (Add and Replace) When the link mode is “Unlink”, use these two buttons at the top of the ChemDraw panel to either add to or replace the content of the Model window. The following table describes the elements of the 3D to Draw Measurement table. When the link mode is “Unlink”, use this button to display the content of the Model window in the Table Element Description ChemDraw panel. Any content that was in the ChemDraw panel is replaced. Column Heading Contains field names describing the informa- The Model Information Panel tion in the table. The Model information panel contains a set of Record Selector Enables you to select an tables whose data provides detailed information entire record. Clicking a about your model. You can display one or more of record selector highlights the following tables in the area: the corresponding atoms • Model Explorer in the model window. •Measurements Field Name Identifies the type of • Cartesian information in the cells •Z-Matrix table with which it is associ- •Atom Table ated. Tables are linked to the structure so that selecting Column Divider Changes the width of the an atom, bond, or angle in either will highlight column by dragging. both. You can edit or paste values to and from Cell Contains one value of one other documents (such as text or Excel work- field in a record. All sheets), and the changes are displayed in the struc- records in a given table ture. contain the same number of cells.

Chem & Bio 3D 11.0 15 User Guide model

key. . Clear Backspace or Contain information all by used Contain information about a spe- Delete Rememberinformation that in theOutput window •Measurement table table •Measurement •Z-Matrix • Internal coordinatestable •Press the the •Press • and Right-click choose Internal and External Tables of parameter types Chem & Bio 3D 11.0 uses two tables: Internal tables. model. Thesecific include: view an internal the table from choose table, To the View menu. External tables. models. Examples of external are: tables NOTE: window is saved.the Comment in Basics Model Building Chem & Bio 3D 11.0 applies create models, As you standard parameters from external tables along the settings to produce with user-selected is not saved when you saveModel. However, the information you is not saved when You can remove informationremove can the Output from You model. the affecting without window messages: remove To 1. to delete. want the text you Select 2.one of the following: Do display. There are several options for selecting your There options for selecting your are several display. desired settings: can display change you defaults in or toolbar use menu the Model Settings dialog box, (right- menus use context-sensitive or commands, can also You in the Model Explorer. menus) click coordinates. and change model view . Copy to to Copy Copy from the con- . Select All All Select . View>Comments box View>Comments . 16 Chapter 1 Export Comments want to save. want to save. and save it in either text or HTML format.and save Alternately, you can choose can choose you Alternately, 2. you box content in the Comments the Select 3. and select box comments in the Right-click 3. the file. Save Exporting comments How- file. the model with All comments are saved can also exportfile or you a as comments ever, copy them to the Clipboard. export to file: comments To 1. Go to Thereports Output box calculations on any data mightyou performmodel; the Comments on your may you or notes comments any enter lets you box Theand Comments boxes Output keep. to want Model window. the found below are typically 3D Chem & Bio a file, and close save When you output. There-but discards comments your saves information to save want if you in the output fore, copy it to the comments box. will need to you box, To save output: 1. you highlight the content the Output box, In 2. and select in the Output box Right-click Output and Comments and Output 4.file for the enter a name As window, In the Save copy output to the Clipboard: To 1. to save. want you Select the text 2. and choose in the window Right-click text menu. 3. choice. of your into the document Paste to restore informationPaste – Copy use must You file. a saved from

Administrator • Elements, Atom Types, and Substructures Model Display tables that you use to build models. Figure 1.12 shows the cylindrical bonds display • Torsional Parameters tables that are used by type (rendering type) with element symbols and Chem & Bio 3D when you perform an MM2 serial numbers displayed. computation. Figure 1.12: Model display • Tables that store data gathered during dihedral driver conformational searches. To view an external table, go to View>Parameter Tables. Then choose the table to view. For more information on Parameter Tables, see Appendix F: “Parameter Tables”. Viewing Options You can superimpose multiple tables if you attach them to an edge of the GUI. One table will be visible and the others will display as selection tabs. Attached tables have the auto-hide feature. To auto-hide a table, push the pin in the upper right To specify the rendering type, do one of the fol- corner of the table. The table minimizes to a tab lowing: when you are not using it. •Go to View>Model Display>Display Mode, and Standard Measurements select a rendering type. Standard measurements are the optimal (or equilib- • Activate the Model Display toolbar, click the rium) bond lengths and angles between atoms arrow next to the Model Display icon and based on their atom type. The values for each par- select a rendering type. ticular atom type combination are actually an aver- • In the Model Settings dialog box, choose Model age for many compounds each of which have that Display, and select a rendering type. atom type (for example, a family of alkanes). Stan- dard measurements lets you build models whose To display serial numbers and element symbols, do 3D representation is a reasonable approximation one of the following: of the actual geometry when other forces and •Go to View>Model Display and click Show Serial interactions between atoms are not considered. Numbers or Show Atom Symbols. Model Settings • Activate the Model Display toolbar and click the Atom Labels and Serial Numbers icons. You can modify certain settings for a model using • In the Model Settings dialog box, select the the Model Settings control panels. Go to Model Display tab, and check the box next to File>Model Settings and select one of the tabs at the Show Element Symbols and Show Serial Numbers. top of the dialog box. The serial number for each atom is assigned in the order of building. However, you can reserialize the

Chem & Bio 3D 11.0 17 User Guide these atomsthese selected are they are displayed in yellow Figure Model label 1.15: Figure the dihedral atoms, select four adjoining If you two select label. If you appears in the model angle the distance bonded or non-bonded atoms, those atoms appears. between Figure 1.14: Bond labels Bond 1.14: Figure The data changes model to reflect the atoms that when three example, For model. the are selected in contiguous atoms H(3)-C(1)-C(2) are selected, the its point to and includes the atom you label model the atom other type, atoms in the selection, and the angle. ation see “Serial Num- see “Serial ation 18 Chapter 1 When you point to a bond, the label displays the bond, point the label displays to a When you andbond length order. bond the the model label for 1.14 shows Figure C(1) and C(2). between Figure 1.13: Atom labels 1.13: Figure Model Data Labels point Whento an atom, you information the about By labelatom appears in a model pop-up window. default, this information includes the element sym- and formal atom type, charge. serialnumber, bol, C(1)the for the model label 1.13 shows Figure ethane. atom of atoms. For more inform For atoms. bers” on page 75. The Elements the symbol comes from element is also The element for an default color used table. more informa- For the Elements defined in table. Element” on page see “Coloringtion, by and 48 “The on Elements” page 203.

Administrator To specify what information appears in atom, to View> Parameter Tables.>Chem 3D Building Atom bond, and angle labels: Types. 1. Go to File>Preferences. Rectification 2. Select the Pop-up Info tab. Rectification is the process of filling open valences 3. Select the information you want to display. of the atoms in your model, typically by adding 4. Click OK when finished. hydrogen atoms. Atom Types To rectify automatically as you build, do the following: Building types contain much of the Chem & Bio 3D 11.0 intelligence for building models with 3D 1. In the Model Settings dialog box, select the geometries. If a building type is assigned to an Model Building tab. atom, you can see it in the model data when you 2. Check the Rectify checkbox. point to it. In the previous section, the selected Bond Lengths and Bond Angles atom has a building type of “C Alkane”. You can apply standard measurements (bond An atom that has a building type assigned has a lengths and bond angles) automatically as you build defined geometry, bond orders, type of atom used or apply them later. Standard measurements are to fill open valences (rectification), and standard determined using the atom types for pairs of bond length and bond angle measurements bonded atoms or sets of three adjacent atoms, and (depending on the other atoms making up the are found in the external tables Bond Stretching bond). Parameters.xml and Angle Bending Parameters.xml. The easiest way to build models uses a dynamic assignment of building types that occurs as you The Model Explorer build. For example, when you change a single bond The Model Explorer lets you explore the structural in a model of ethane to a double bond, the building features of a model, such as chains and functional type automatically changes from C Alkane to C groups. The Model Explorer is also useful for Alkene. In the process, the geometry of the carbon when you want to alter a model’s properties. and the number of hydrogens filling open valences changes. You can also build models without assign- The Model Explorer is designed as a hierarchical ing atom types. tree control that you can expand and collapse as necessary and view any part of the model you To assign building types as you build: want. Changes are applied in a bottom-up manner, 1. In the Model Settings dialog box, select the so that changes to atoms and bonds override Model Building tab. changes at the chain or fragment level. Display 2. Check the Correct Atom Types checkbox. modes and color settings are easy to control at a fine-grained level. Properties of atoms and bonds To assign atom types after you build: are also easy to access and change. You can 1. Select the atom(s). show/hide/highlight features at any level. Hidden 2. Go to Structure>Rectify. or changed features are marked in the tree with Building type information is stored in the Building colored icons, so you can easily keep track of your Types table. To view the Building Types table, go modifications. See “Model Explorer” on page 99 for more information.

Chem & Bio 3D 11.0 19 User Guide in the . or .cc2), then edit that or .cc2), then dinates in this directly Apply Standard Measurements Apply Standard tab of the Model Settings dialog while you you while tab of the Model Settings dialog and Structure>Measurements If you edit coordinates in the table, remember to the table, in edit coordinates If you Rectify The Measurement Table The Measurement bond lengths, The displays Measurement table and ring closures. angles, dihedral bond angles, itwill Table, first open a Measurement When you be blank. Table: in a Measurement data display To 1. Go to 2.information Select the wish to display. you display- table, Measurement the Figure 1.18 shows ing the bond lengths and bond angles for ethane: NOTE: Model Building that other atoms areedit so not affected. for of the Cartesian example An coordinates, 1.17. in Figure is shown ethane, Cartesian coordinates 1.17: Figure turn off Instead of editing the coor editing the of Instead the Cartesian using the model save can you table, coordinates file format (.cc1 and paste can also copy You with a text editor. file using worksheet or Excel file text a the table into the in the context commands menu. (right-click) submenu submenu Struc- View>Z-Matrix View>Z-Matrix Model Position . You can copy and paste tables to can copy . You . You can edit the values within the table, or table, within the can edit the values . You 20 Chapter 1 text files or Excel spreadsheets using the com- using the spreadsheets Excel text files or menu. mands in the context (right-click) an example of the internal1.16 shows coor- Figure dinates (Z-matrix) for ethane: Cartesian Coordinates Cartesian coordinates describeatomicin position to an Z-coordinates relative and terms of X-, Y-, arbitrary origin. Often, the origin correspondsto can set the ori- you However, the first atom drawn. gin using commands in the Figure 1.16: Internal coordinates for ethane 1.16: Internal coordinates Figure Internal are oftena model coordinates forreferred commonly used Z-matrix and are the most to as a coordinates for preparing a model for further com- to enter you a Z-matrix allows putation. Changing angles and specifying atoms by between relations lengths. go the Z-Matrix table, display to To Table Each atom in a model occupies a position in space. atom model in a a position occupies in space. Each to represent the posi- ways two there are Typically, atom:aninternal tion of and Cartesian coordinates establishescoor-the& Bio 3D Chem coordinates. build model. a dinates as you Z-matrix Model Coordinates Model of the Structure menu. ture>Set Z-matrix move atoms within the model and go to move

Administrator Figure 1.18: The Measurement table Actual values as closely as it can to the Optimal values. If you edit the Actual field, you change the value in the model, and the atoms in the model move to represent the new values. If you edit the Optimal value, you apply a constraint. These values are used only in Clean Up (on the Structure menu) and MM2 computations. Deleting Measurement Table Data You can isolate the information you enter in the Measurement table by deleting the records that you do not want to view. For example, you could display bond lengths, then delete everything except the carbon-carbon bonds. This would make them easier to compare. To delete a record, right-click the record and click Actual vs Optimal Values Delete on the context menu. Optimal values are the ideal measurements for your model. These values are based on model NOTE: Deleting records in a Measurement table does not building parameters that come with Chem & Bio delete the corresponding atoms. 3D 11.0. The Actual values are the measurements from your model. When you perform a structure To clear the entire table, go to Structure> Measure- clean up, Chem & Bio 3D 11.0 tries to match the ment and select Clear.

Chem & Bio 3D 11.0 21 User Guide 22 Chapter 1

Administrator Chapter 2: Tutorials

The tutorials offers several examples of some basic Setting the Model Display tasks you can perform with Chem & Bio 3D 11.0. We start by illustrating how to use the ChemDraw To view models as shown in this tutorial: Panel to create a basic model. From there, we 1. Go to View>Toolbars>Model Display. describe how to display orbitals, map surfaces, and 2. On the Model Display toolbar, select the Display a variety of other useful features. Mode dropdown menu and choose Cylindrical Bonds. NOTE: For examples of MOPAC calculations, see Chap- Figure 2.1: Setting the model display mode ter 10, “MOPAC Calculations” on page 131.

Tutorial 1: The ChemDraw Panel In this tutorial, you build a model of phenol by drawing it in the ChemDraw panel. When you link the ChemDraw panel to the Model window, your Building a Phenol model two-dimensional structure will automatically be transformed into a 3D model. 1. Go to File>New to open a new model window (if one is not already opened). Dual Link Mode 2. Go to View>ChemDraw Panel to open the Chem- Before you draw the structure, you will first want Draw panel. to create the link by selecting the Dual Link icon ( ) at the top of the ChemDraw panel. “Dual” TIP: The ChemDraw panel is automatically hidden by means that the ChemDraw panel and Model Win- default. If you want the panel to stay open, push the pin on dow are linked such that what you create in one the upper right. also appears in the other.

Setting Defaults 3. Click in the ChemDraw panel. The ChemDraw tools palette appears. In addition to creating the link, you may also want to use the default settings: 4. On the ChemDraw tools palette, select the Ben- zene tool. 1. Go to File>Model Settings. 5. Click in the ChemDraw panel to place a benzene 2. In the Model Settings dialog box, click the Reset to ring. The ChemDraw structure is converted to a Default button. 3D representation. 3. Click the OK button.

Chem & Bio 3D 11.0 23 User Guide Chapter 2 Chapter .

in any direction to rotate the The Trackball tool rotates the view only;it does The Trackball If you are using default settings, hydrogens are hydrogens aredis- If you usingdefaultsettings, model. hold down the mouse button. the mouse hold down the edge of the window, over mouse you As dow. the rotation bars appears. release the mouse button. A model of ethane button. A model release the mouse appears. Rotating models model, see the three-dimension features of your To have tool. You can rotate it using the Trackball you free-hand;therotating X, Y, around of by choice a select. around a bond that you or Z axis; or, perform rotation: free-hand To 1. tool the Trackball Click 2. . and center of the model window the near Point 3. Drag the cursor NOTE: not change atoms’ Cartesian coordinates. axis an Rotating around rotate around an axis: To 1.edgethe win- the cursor to of the model Move Tutorial 2: Using Bond Tools Bond 2: Using Tutorial to dem- a model of ethane use we In this tutorial, someonstrate of fundamental features of the to rotate how show 3D 11.0. We Chem & Bio serial atom add and view bond properties, models, numbers. 1.tool the Single Bond Click 2. drag to the right and in the Model window, Click NOTE: automatically. played key. Enter in the text box, then press the then press the text box, in OH Use Ctrl+A to select the model you want to copy. want you the model to select Use Ctrl+A text box appears. text box The phenol molecule is displayed in the Model Theis displayed phenol molecule panel. ChemDraw the and inwindow TIP: Unlink Mode can turn you hot off theby want, linking If you button the Unlink at the top of the Chem- clicking will need to use the you do this, panel. If you Draw to copy models buttons and Draw>3D 3D>Draw linking more on the For windows. the between see “Linking panel and Model window, ChemDraw on pagewindows” 15. To change the benzenering to phenol: To 1.A in the 3D model. hydrogen any Double-click 2. Type Figure 2.2: A 3D model of benzene of benzene model 2.2: A 3D Figure 24

Administrator 2. Drag one of the bars to rotate the model around 3. Move the pointer over the C-C bond to display that axis. its bond length and bond order. Figure 2.4: Viewing bond length NOTE: Rotation bars are available only when you use the Trackball tool.

Rotating around a bond To rotate around a bond: 1. Click the Select tool. 2. Select the bond you want to rotate the model around. 3. Select the Trackball tool. To display information about angles, select several 4. Click and drag the Rotate About Bond rotation bar atoms. on the left side of the Model window. 1. Click C(1), then Shift+click C(2) and H(7). Examining Models 2. Point to any of the selected atoms or bonds. Here we view some bond properties of the ethane The angle for the selection appears. model: Figure 2.5: Viewing bond angles 1. Click the Select tool. 2. Move the pointer over the left carbon. An information box appears next to the carbon. The first line contains the atom label, either C(1) or C(2). The second line contains the name of the atom type, C Alkane. Figure 2.3: Viewing the atom label

To display information about adjacent atoms: 1. Hold the Shift key and select four adjacent atoms. 2. Point to any portion of the selection. The dihedral angle formed by the four selected atoms is displayed.

Chem & Bio 3D 11.0 25 User Guide . Chapter 2 Chapter . Set Bond Order>Single Set Bond View>Model Dis- View>Model bond appears. below. as shown bons Create a ring: Hiding Hydrogens hydrogen the to hide want may you Sometimes, The building easier. model to make atoms in your just active, there and chemically still are hydrogens not in view. go to hide the hydrogens, To Adding atoms a create to add more atoms to the model Here we cyclohexane ring: 1.tool the Single Bond Click . 2. Dragfrom upward the left carbon. Another C-C 3. six car- have untilyou adding bonds Continue play>Show Hydrogen play>Show atoms>Hide 3. go context In the menu, to ng a dihedral angle a dihedral ng decreases and the bond order increases. Building Cyclic Compounds model ethylene the building on can continue You to create cyclohexane. First, change ethylene back to ethane: 1. tool the Select Click 2. the double bond. Right-click . Figure 2.7: Model of ethylene. Figure If you want, you can also change the bond order. can also change the bond order. you want, If you can change the ethane model we to In this case, ethylene: 1. tool Bond the Double Click . 2.C(2). C(1) to the mouse from Drag 3. to the C(1)-C(2)bond. The bond length Point Figure 2.6: Viewi 2.6: Figure 26

Administrator 1. Drag from one terminal carbon across to the 2. Go to View>Model Display>Show Atom Symbols, other. or click the Atom Symbol icon on the Model Display toolbar.

NOTE: The serial numbers that appear do not reflect a normal ordering because you started with a smaller model and built up from it.

If you want, you can change the numbering order by choosing which atom is numbered first. To renumber the atoms:

2. Release the mouse button to close the ring. 1. Select the Text Building tool . Figure 2.8: Building cyclohexane with the bond tool 2. Click the first atom. A text box appears on the atom. Figure 2.9: Adding atom symbols and numbers

3. Type the number you want to assign to this atom (1 for this example). 4. Press the Enter key. The first atom is renumbered as (1). Serial Numbers and Labels 5. Double-click each of the atoms in the order you Whenever you build or examine a model, atoms of want them to be numbered. the same type all look the same (as they should). 6. Go to View>Model Display>Show Hydrogen However, it is sometimes convenient to be able to atoms>Show All and examine the model using the distinguish one from another as you work. This is where atom serial numbers and labels become use- Trackball Tool . ful. Structure Cleanup 1. Go to View>Model Display>Show Serial Numbers As you build a model, you may accidentally distort or click the Serial Number icon on the bond angles and bond lengths. To correct for this: Model Display toolbar. 1. Go to Edit>Select All. All the atoms in the model are selected. 2. Go to Structure>Clean Up.

Chem & Bio 3D 11.0 27 User Guide Chapter 2 Chapter . . . File>Save As tut2a Save Notice that the “C” you entered you the “C” previously that Notice the in click click rotate your model to get model a betterviewrotateyour of what are building. you groups. them to methyl Save a copy of the model using the name tut2b. the a copy of Save in model will be used of your copies These two later tutorials. 2. Type Text tool remains as the default until you change it. You only You remains it. change tool you until as the default Text Saving the File When the minimization is complete: 1. Go to Models Using Labels to Create typing atom can also create models labels by You in a text box. numbers) (element symbols and shown to build 4-methyl-2-pentanol example, For below: TIP: and pressEnter key. have the double-click, to refine the structure to an energy to minimum Now, into account the additional interactions take the MM2 Click groups. the methyl by imposed toolMinimize Calculation on the toolbar. 3. Select the file a directoryand to save in which You don’t have to select the Text tool to use it. to use tool Text the to select have don’t You other with any has tool selected Double-clicking the as same effect the Text with single-clicking hydro- more replace two demonstrate this, To tool. gensmethod: an alternative using 1. tool Select the Trackball can you so that 2. to change more hydrogens two Double-click key. Enter . g Cyclic Compounds” on Cyclic Compounds” g . . in the text box at the bottom of the at the bottom box in the text File>Close Window File>Save Element symbols and substructure names are case Save tut1 dialog box. box appears. box 4. Click 2. file. the directorya Select to save which in 3. Type atom. to C(1) is changed to a car- attached The hydrogen bon. If rectification is turnedcarbonthe on, hydrogens. is saturated with valence NOTE: page 26. change a hydrogen Using the cyclohexane model, atom into a carbon atom: 1.Building tool the Text Click 2.C(1).to A text attached atom . hydrogen a Click 3. “C” uppercase and press the Type This methods to build alternative tutorial illustrates you Before tool. Building models using the Text are you If of cyclohexane. begin, build a model see “Buildin unsure how, Replacing Atoms Tutorial 3: The Text Building Tool Building 3: The Text Tutorial Saving the model Saving want may you to next tutorial, the moving Before model. your close and to save 1.to Go 5.it. to activate window the model Click 6. Go to sensitive. You must typean uppercase must C to create a carbon sensitive. You 28

Administrator Figure 2.10: Creating a model with the text box 1. Right-click an empty space in the ChemDraw panel and select Structure>Convert Name to Struc- ture in the context menu. 2. In the Insert Structure dialog box, type Pentane and click OK. A drawing of pentane appears in the ChemDraw panel. 3. So that pentane appears in the Model window, ensure that Dual Mode is selected at the top of the ChemDraw panel. 4. In Chem & Bio 3D 11.0, click the Single Bond 1. Go to File>New or click the New tool on the tool . Standard toolbar. 5. Draw two bonds, one off the second carbon and 2. Click the Text Building tool . another off the fourth carbon in the pentane chain. 3. Click in the empty space in the model window. A text box appears where you clicked. 6. Using the Text tool, select one of the carbon atom extending from the C(2) carbon and 4. In the text box, type: change it to O. CH3CH(CH3)CH2CH(OH)CH3. 7. Go to Edit>Select All. You type labels as if you were naming the struc- 8. Go to Structure>Clean Up. ture: pick the longest chain of carbons as the backbone, and specify other groups as substituents. If you want a more accurate representation of a Enclose substituents in parentheses after the atom low energy conformation, optimize the geometry to which they are attached. of the model by clicking the MM2 Minimize tool 5. Press the Enter key. on the Calculation toolbar.

TIP: You don’t have to click the Select tool every time you TIP: The Text building tool also accepts structures in want to select something. Just hold down the letter S on your SMILES notation, either typed in or cut and pasted from keyboard while working with any building tool, and you tem- other documents. porarily activate the Select tool.

Name=Struct Stereochemistry Another, simpler way of building this model is to You cannot specify stereochemistry when you type Pentane in the ChemDraw panel build models with labels. For example, 1,2-dime- Name=Struct text box, then modify the appropri- thyl cyclopentane appears in the trans conforma- ate hydrogens. tion by default. However, you can modify the To create the model using Name=Struct: default structure to show the cis-isomer.

Chem & Bio 3D 11.0 29 User Guide Chapter 2 Chapter key. Enter Enter actly as it appears in the Sub- actlyin the appears as it and press the press and . . key. A model of nitrobenzene model A key. in the text box. Enter File>New File>New Ph(NO2) H(Ala)12OH Predefinedsubstructures arethe substruc- listed in appears. text box appears. text box forms. The substructure in this example is the phenyl “Ph”. Substructuresby as indicated are group, defined withpoints specific for attachment other point is phenyl, the attachment For substituents. C(1). Build a peptide model: 1. Go to 5. the Press tures.xml file. To view the list, go to View>Parameter go to View>Parameter view the list, tures.xml file. To is case type in the text box you Text Tables>Substructures. typeit ex must sensitive (you 2.Building tool the Text Click 3. A window. the Model in . an empty space Click 4. Type the model Viewing Change type: the model display TIP: structures table). substruc- using a nitrobenzene of build model To tures: 1. Go to 2.Building tool the Text Click 3. . window. the Model in the empty space Click 4. Type 5. this structurehelix that Rotate to see the alpha Over 200 substructuresOver predefined are & in Chem These11.0. Bio 3D commonly the most include used organic structures. . isomer: cis- -isomer appears. . trans . . . key. The key. . Enter Structure>Invert Edit>Select All Edit>Select Up Structure>Clean File>New C(1) CH(CH3)CH(CH3)CH2CH2CH2 -isomer appears. You can rotate the model You -isomer appears. cis Now invert it t show to display the to display itt show invert Now 1. tool the Select Click 2. Select . 3. Go to The The isomers after the differences between the to see the molecule. invert you 5. the Press Using Substructures structures. simple building Labels are useful for more complex structures, larger, to make However, to use a combination of find it easier may you predefined substructures. labels and To illustrate, first, build the default structure: illustrate, To 1. Go to Figure 2.11: More complex models with the text box the text models with complex More 2.11: Figure 2.Building tool Text the Click 3.model window. the in . space in the empty Click 4. Type 6. Go to 7. Go to 30

Administrator 1. Click the arrow on the right side of the Tutorial 4: Examining Model Display Mode tool on the Model Display Conformations toolbar. 2. Select Wire Frame as the Model Type. This tutorial uses steric energy values to compare the two conformations of ethane—eclipsed and staggered. TIP: You can also click the Display Mode icon. Successive To draw ethane: clicks cycle through the Display Mode options. 1. Open the ChemDraw panel if it isn’t already open. 3. Select the Trackball tool , and rotate the 2. Draw a line in the ChemDraw panel. A model of model so you are viewing it down the center of ethane appears. the helix as shown in Figure 2.12. Viewing Bond Properties Figure 2.12: Rotating a model with the trackball To view the bond properties: 1. Click in the Model Window 2. Go to Structure>Measurements>Generate All Bond Lengths. The Measurement table appears. 3. Go to Structure>Measurements>Generate All Bond Angles.

NOTE: If the Measurement table appears along side the Model Explorer, you can stack the windows by locking the Model Explorer window open and dragging the Measure- ment table on top of it.

The bond lengths and bond angles for ethane 4. Use the Model Display Mode tool to choose Rib- appear in the Measurement table: bons as the model type to see an alternative display commonly used for proteins. • Display–Select or deselect checkboxes in this column to display the measurement in the Figure 2.13: Ribbon display model. • Atoms–This column indicates the atoms to which each measurement applies. • Actual–This column displays the measurements for the model in the active window. If you distort the model (or any part of it), the values in this column change automatically. • Optimal–This displays measurements (for bond lengths and bond angles only) that represent the standard measurements for the mole-

Chem & Bio 3D 11.0 31 User Guide . Chapter 2 Chapter Steric and ompute Properties ormation, then compare it dialog box appears. The appears. dialog box Pi Bond Orders Pi Bond selected as the default. If it does selected . box appears beneath the model win- beneath appears the model box Calculations>MM2>C The values of the energy of the The values terms can vary slightly Run Use Shift-click to select multiple properties.Use Shift-click Compute Properties Output The The Energy Summary Energy 2. Click not, select them. not, select TIP: NOTE: processorthe computer based on areyou using. Dihedral Angles conformationobtain the eclipsed of ethane, To angle (torsional angle). Thisrotate a dihedral is you Figure 2.15: Ethane in stable conformation stable in Ethane 2.15: Figure calculate the this result examine numerically, To steric energy conf of this to a higher energyconformation: (eclipsed) 1. Go to Properties shows tab dow, with Steric EnergySteric with The last results displayed. dow, energy. the total line displays This staggered conformation, where the hydrogens distance maximum a are carbons on adjoining representsfrom one another (which the global a potential on energy minimum represents plot) conformationthe most stable of ethane. The The cule the model represents. If you clean up a up clean you If model represents. the cule distorted tries to 3D 11.0 & Bio Chem model, that Actual values the model such modify the as closely possible. as values the Optimal match ethane. 3. Stop dragging an end-on view of have when you [ Newman projection of ethane projection Newman into orient a Newman the ethane model we Now, projection to betterconforma- illustrate the two tions. rotate the ethane model: To 1. tool the Trackball Click 2. . the model. and drag to rotate Click theof the (bottom left statusdrag, bar As you details about the rotation: screen) shows Chem & Bio 3D 11.0 shows the most common the 11.0 shows Chem & Bio 3D rotatecan parts conformation You molecule. of a other to see group, a methyl as such a molecule, of conformations. Figure 2.14: The Measurement Table 2.14: The Measurement Figure . 32

Administrator is a common way to analyze the conformational Figure 2.17: Rotating a dihedral angle space for a model. To view dihedral angles: 1. Go to Structure>Measurements>Generate All Dihe- dral Angles. All of the model’s dihedral angles are added to the bottom of the Measurement table. 2. In the Measurement table, select the Display checkbox for the H(3)-C(1)-C(2)-H(8) dihedral to select the corresponding atoms in the model. In the Measurement table, notice that the dihedral To help keep visual track of the atoms as you for H(3)-C(1)-C(2)-H(8) is now minus 0 degrees, as change the dihedral angle you can display the serial shown in the Measurement table. numbers and element symbols for the selected Figure 2.18: The Measurement table atoms. 1. Go to View>Model Display and select Show Serial Numbers and Show Atom Symbols. 2. Click the arrow next to the Trackball tool, and tear off the rotation dial by dragging on the blue bar at the top. 3. At the bottom of the Rotation Dial, select the dihedral rotation button. Figure 2.16: The Rotation dial To compute steric energy: trackball 1. Go to Calculations>MM2>Compute Properties. local axis rotation dihedral rotation NOTE: The property tab defaults should remain as in the dihedral, move other previous calculation. side

4. Click and drag the green indicator button to 2. Click Run. rotate the dial to 0.0. The final line in the Output box appears.

Chem & Bio 3D 11.0 33 User Guide Chapter 2 Chapter Driver>Single Angle Angle Driver>Single lick and drag across the lick Calculations>Dihedral Calculations>Dihedral The dihedral is rotated in 5-degree increments Plot. rotates the dihedral to the selected conforma-the rotates tion. c of rotation angles, Chartitself. while viewing the model or energy setting). 2. Thepoint of interest. a model display Click 3. the conformation see energy through a range To NOTE: the Outputin each point window. angle (other end of the rotate the other dihedral To window Dihedral in the bond), Driver right-click other End. Rotate and choose Rotating two dihedrals dihedrals: rotate two To The Dihedral Driver Chart opens. When the com- the When ChartThe opens. Driver Dihedral is completed, a graphputation showing displayed is the energy of rotation angle the versus (kcal) carbon-carbonaround the bond. view the conformation point: given at any To 1.degree (specific location a In the chart,to point the move you As appears. A dashed-line box on a specific point define to moves the box mouse, the graph. Using the 2.20: driver dihedral Figure through 360 degrees72conformationsof for a total to pro- can view the minimized energy for values duce the graph. You 3. Go to The dihedral driver featureonly in is available As a rule, steric energy should only values be used The values of theenergy of The values terms can vary slightly NOTE: 11.0 and Chem3DUltra ProChemBio3D 11.0. a single angle plot demonstrate we In this tutorial, on ethane. using the dihedral driver use the dihedral driver: To 1.model of ethane. Build a 2.carbon-carbonthe model. Select bond in your The dihedral driver lets you map the conforma-you lets The dihedraldriver dihe- varyingone or two space of a model by tional the model dihedral angle value, At each dral angles. energy force field and the MM2 is minimized using the steric energycomputed and model is the of you graphed. complete, is After the computation with the data to locate the models the can view energy steric use these and as startinglowest values points for further refinement in locating a stationery point. NOTE: for differentcomparing conformations of the same model. 5: The Dihedral Driver Tutorial NOTE: type of computer processorbased on the are you using. The steric energy for the eclipsed conformation is greater(~3.9 kcal/mole) in energy than that of the staggered conformation (~1 kcal/mole), indi- that the staggeredcating configuration is the con- formationexist. to more likely is that Figure 2.19: Output The 2.19: box Figure 34

Administrator 1. Use Shift+click to select two adjacent bonds. Tutorial 6: Overlaying Models In this case, the middle atom’s position remains Use overlays to compare the structural similarities fixed between models or conformations of the same 2. Go to Calculations>Dihedral Driver>Double Angle model. Plot. Chem & Bio 3D 11.0 provides two overlay tech- The Output window opens. When the computa- niques: tion is completed, a graph is displayed showing •A fast overlay algorithm theta 1 vs. theta 2. • A manual method based on minimization cal- Figure 2.21: Two dihedrals in the dihedral driver culations

NOTE: Fast Overlay is available only in ChemBio3D Ultra 11.0 and Bio3D Ultra 11.0.

This tutorial describes the fast overlay method. For the minimization method, see “Comparing Models by Overlay” on page 97. The minimization method is more accurate, but the fast overlay algorithm is NOTE: The chart is the result of rotating one angle through more robust. In both tutorial examples, you super- 360° in 15° increments while holding the other constant. The impose a molecule of Methamphetamine on a mol- second angle is then advanced 15° and the operation is ecule of Epinephrine (Adrenalin) to demonstrate repeated. their structural similarities. 1. Go to File>New. To view the conformation at any given point, click 2. Go to View>Model Explorer (if the Model any block in the chart. The model display rotates Explorer is not already open). both dihedrals to the selected conformation. 3. Choose the Text tool from the Building Toolbar Customizing the chart and click in the model window. A text box Right-click the chart to set the rotation interval appears. used for the computation. You can also select dis- 4. Type Epinephrine (be sure to use capital ‘E’) and play colors for the chart, background, coordinates, press the Enter key. A molecule of epinephrine and labels. appears. You also use the context menu to copy the chart, 5. Click in the model window again to open or its data set, to other applications, or save the another text box. data. 6. Select the entire word Epinephrine, replace it with Methamphetamine, and press the Enter key. Methamphetamine appears in the Model Explorer.

Chem & Bio 3D 11.0 35 User Guide Chapter 2 Chapter Overlay>Set on the context menu. on the context . Overlay>fast overlay Overlay>fast Target Fragment Methamphetamine fragment. region of the model window to ensure all frag- to ensure all modeltheregion window of ments are deselected. nephrine fragment to select it. Figure 2.24: Model Explorer with target selected selected with target Model Explorer 2.24: Figure 4. the right-click In the Model Explorer window, 5. Go to Figure 2.23: Rotating fragments prior to alignment to alignment prior fragments Rotating 2.23: Figure frag- the of which to decide have At this point, you will be the tar- and which to move want ments you get. with only two In this simple example, might, You really matter. it doesn’t compounds, a to overlay want where you cases have however, target.compounds on a specific of number 1. any empty Objects tool, click the Move Using 2. the Epi- click In the Model Explorer window, 3.fragment and gothe Right-click to Thetarget.on the fragment changesto a icon atom in it and using the Shift in it and using atom You can rotate can separately a fragment fromthe whole You ment in the Model Explorer. it. to move drag the model in the model window positionthe of the frag- indicates oval or A box it. are moving ment while you model by selecting at least one by selecting at model tool. Try with the trackball this to re-orientkey the fragments as in the illustration below. the illustration as in TIP: The two fragments may be jumbled together. You You together. be jumbled may fragments The two proceed. to separatemight want them before you a fragment: move To 1. frag- the name of the select a fragment, click To 2. Objects tool Using the Move , Shift-click- Figure 2.22: Two fragments fragments Two 2.22: Figure 36

Administrator The fragments are overlaid. The numbers show the In this tutorial, we demonstrate the Dock com- serial numbers of the target atoms to which the mand using two polymer chains. matching overlay atoms correspond. Build the first polymer chain

TIP: You can also designate a fragment as a target rather 1. Open a new Model window and select the Text than a group. However, either a fragment or group may be Building tool. overlayed. 2. Click in the model window. A text box appears. 3. Type (AA-mon)3(C2F4)4(AA-mon)3H in the text box. Figure 2.25: Overlaid fragments 4. Press the Enter key. A polyacrylic acid/polytetrafluoroethylene block copolymer appears in the model window. The text, (AA-mon)3, is converted to a polymer segment with three repeat units of acrylic acid. The text, (C2F4)4, is converted to a polymer segment with four repeat units of tetrafluoroethylene. Build a copy of the chain Click in the model window well above and to the right of the first model. When the filled text box appears, press the Enter key. A second polymer molecule appears. Orient the chains To turn off the fast overlay mode, go to Over- 1. Click in the empty space in the model window to lay>Clear Target Fragment. deselect any atoms in the model window. Tutorial 7: Docking Models 2. Click the down arrow on the Trackball tool to open the rotation dial tool. The Dock command lets you position a fragment in 3. Select the Y axis, and drag the dial to show 55°. a desired orientation and proximity relative to a second fragment. Each fragment remains rigid during the docking computation. TIP: To get exactly 55° you may need to edit the value in The Dock command is available when two or more the number box. After editing, press the Enter key. The distances between atoms in one fragment and value displayed in the right corner of the dial should be the atoms in a second fragment are specified. These same as in the number box. distances are entered into the Optimal field in the Measurement table. The resulting model appears as shown in Figure You can use docking to simulate the association of 2.26 (the second model may appear in a different regions of similar lipophilicity and hydrophilicity position on your computer): on two proximate polymer chains.

Chem & Bio 3D 11.0 37 User Guide Chapter 2 Chapter value and . . . The Dock dialog box The. box dialog Dock Minimum RMS Error RMS Error Minimum Minimum RMS Minimum Gradient for the Structure>Dock Display Each Iteration for the 0.100 appears. 0.010 AtomsC(98)-C(6)C(104)-C(12) Actual 21.1840C(108)-C(16) 21.2863C(22)-C(114) Optimal 21.1957 5.0000 5.0000 C(28)-C(120) 20.6472 5.0000 C(34)-C(126) 20.7001 5.0000 C(133)-C(41) 20.1410 5.0000 C(45)-C(137) 20.3559 5.0000 C(50)-C(142) 20.3218 5.0000 20.4350 5.0000 5.0000 Figure The Dock 2.27: dialog box Figure 2. Type The computation stops when the RMS docking Errorthe than Gradient becomes less or the RMS RMS Error Gradi- RMS Minimum and Minimum ent value. 3. Click Ignore the distances in the Actual cell because they Ignore the distances in the Actual cell because posi-depend was the second polymer how on sec- the when to the first polymer tioned relative created. ond polymer was computation:begin the docking To 1. Go to

at least AA-mon 21 in Fragment 1 C(6) key. pair. Enter atom in Fragment 2 ( atom in Fragment group. C(98)-C(6) . C(98) . Repeat steps 1 through 6 for match- steps through 1 . Repeat distance determines distance closely the how and press the Structure>Measurements>Display Distance AA-mon 2 5 Optimal Measurement in the group) to select it. CTRL-click and AtomsC(1)-C(93) Actual 21.2034 Optimal 5.0000 3. Go to molecules dock. In this tutorial, you will set the dis- tutorial, you In this dock. molecules tance to 5Å. 1. select In the Model Explorer, 4. Optimal the cell. Click 5. Type Set optimal distances The 2. Locate the Figure 2.26: Docking models Docking 2.26: Figure The Measurement table opens (or becomes active), The Measurement table opens (or becomes active), the displaying four atom pairs For thethroughouting atom pairs fragments. group one pair from each choose if you example, the following: list might look like your The optimal distance between C(6) and C(98) is Thedistance between optimal 5.000Å. specified as specify must you a reasonable dock, have To 38

Administrator This allows you to see how much the fragments ing computation. The distances in the Actual cell have moved after each iteration of the docking are close to the distances in the Optimal cell. computation. Figure 2.30: Measurements for docked polymers 4. Click Start. Figure 2.28: Recording iterations

Your results may not exactly match those described here. The relative position of the two fragments or molecules at the start of the docking computation can affect your results. For more accurate results, iteration lower the minimum RMS gradient. values Tutorial 8: Viewing Orbitals The highest occupied molecular orbitals (HOMO) and lowest unoccupied molecular orbitals (LUMO) Note that while the docking computation pro- are commonly the most important orbitals affect- ceeds, one molecule remains stationary and the ing a molecular reactivity. This tutorial examines second molecule moves. the orbitals of double bonds by looking at ethene, the simplest molecule containing a double bond. To stop the docking computation before it reaches its preset RMS values, click Stop Calculation Create an ethene model: on the Calculation toolbar. Both docking and 1. Go to File>New. recording are stopped. The Status bar displays the 2. Draw a double bond in the ChemDraw panel. A values describing each iteration. molecule of ethene appears. Figure 2.29: Docked polymers Before you can view the molecular orbital surface, you must first calculate it. 3. Go to Calculations>Extended Hückel>Calculate Sur- faces. To view the Highest Occupied Molecular Orbital (HOMO): 1. Go to Surfaces>Choose Surface>Molecular Orbital. 2. Go to Surfaces>Select Molecular Orbital to see the HOMO/LUMO options. Select HOMO (N=6). The following illustration shows the distances The pi bonding orbital surface appears. between atom pairs at the completion of the dock-

Chem & Bio 3D 11.0 39 User Guide

Chapter 2 Chapter 1-propene . The pro- . . File>New Gaussian is available onlyUltra for ChemBio3D is available Gaussian Delete Turn Off Automatic Rectification Automatic Off Turn and click the OK button. A molecule of 1-pro- the OK click and pene appears. using the Select tool. pene radical is displayed. pene radical is panel and goto Structure>Convert to Name Structure. 4. hydrogen select the H6 In the Model window, 5. Press A dialog box appears asking if you want to turn want appears askingA if you dialog box off that, in rectification. Chem & Bioknows 3D 11.0 four substituents. carbon atoms have most cases, 6. Click Next, calculate the minimization: Figure 2.34: Propene radical model Propene 2.34: Figure NOTE: 11.0. Thea textbook is allyl radical of reso- example nance-enhanced stabilization. The allyl radical 2.33: Figure first surfaces, spin density with examine radicals To create the allyl radical: 1. Go to 2. of the ChemDraw area in an empty Right-click 3. In the Insert Structure type box, text mization using CS MOPAC or extended Hückel extendedor Hückel CS MOPAC using mization calculations. . The pi antibond- Surfaces>Molecular LUMO(N=7) You may need to rotate may need to molecule to view the the You and Select and Orbital ing orbital surface appears. Tutorial 9: Mapping Surfaces Tutorial This tutorialdemonstrates Gaussian minimization to molecular sur- to map calculated values and how can perform mini- the same You faces for viewing. These of many different are orbitals only avail- two The othersrepresent interactionsable. of various sigma orbitals. Figure 2.32: Pi antibonding orbital surface orbital surface Pi 2.32: antibonding Figure orbitals. orbitals. go3. to the LUMO, view To NOTE: Figure 2.31: surface orbital 2.31: Pi bonding Figure 40

Administrator 1. Go to Calculations>Gaussian Interface>Minimize 1. On the Surfaces toolbar, point to Surface and (Energy/Geometry). select Total Charge Density. The icon changes to 2. In the Routine tab, set the method to PM3, and denote the surface selected. the wave function to U-Unrestricted Open-Shell. 2. On the Surfaces toolbar, point to Display Mode 3. Also in the Routine tab, set the Spin Multiplicity to and choose Translucent. 2. 3. On the Surfaces toolbar, point to Color Mapping and choose Spin Density. NOTE: If you are doing this tutorial with CSMOPAC, 4. On the Surfaces toolbar, choose Isocharge. The there is no Spin Multiplicity setting. Isocharge tool appears. Figure 2.36: Using the Isocharge tool

Setting the Spin Multiplicity ensures that the molecule is a radical. One of the best ways to view spin density is by mapping it onto the Total Charge Density surface. This allows you to see what portions of the total charge are contributed by unpaired electrons, or 5. Set the isocharge to 0.0050. (The number in the radicals. middle is the current setting.) To view spin density mapped onto the total charge density surface: NOTE: The isocharge is used to generate the surface. You can adjust this value to get the display you want. The illus- 1. In the Properties tab, select Molecular Surfaces and tration below was made with the setting of 0.0050. Spin Density. 2. Click Run. When the calculation is finished, select the Track- Figure 2.37: Viewing the total charge density surface ball tool and rotate the model back and forth. It should be completely planar. Figure 2.35: Viewing the minimized model

To complete this tutorial, you will need to adjust a Most of the surface is grey, indicating that there is number of surface settings. For convenience, acti- no contribution to it from unpaired electrons. The vate the Surfaces toolbar. Go to View>Toolbars>Sur- areas of red centered over the terminal carbons is a faces. visual representation of the expected delocalization

Chem & Bio 3D 11.0 41 User Guide Chapter 2 Chapter lized charges for all atoms in mputed by Extended mputed by Chem & Bio 3D 11.0 recognizes formal charges Hückel. NOTE: delocalized charges,a chargedhover the mouse over atom. MOPAC, Using the theories in Extended Hückel, can compute the partialor Gaussian, charges you the partialexample, the following In atom. for each charges forco phenolare you assign to atoms in the model window and ChemDraw and the model window assign to atoms in you calculatesdelocapanel. It then displayformal To wheremodel and delocalization occurs. the In Chem & Bio 3D 11.0, some atoms have non- 11.0, 3D & Bio In Chem atoms have some the two example, For integral charges. delocalized charges have each atoms in nitrobenzene oxygen across is one electron shared because there -0.5 of quantum more accuracy, For bonds. N-O the two calculations can producemechanics partial charges are also non-integral). (which 9, electrons in mol- Tutorial in as shown However, molecule that actually occupy areas of the ecules and can atoms are notindividual associated with they as attractednucleii also be to different atomic fact, In across different atomic orbitals. move of bonds are a representationmovement the of different atomic nucleii. between these electrons of a do not occupy the orbitals electrons Because of each charge the actual molecule, singleatom in a atom is not integral, on the average butis based occupy- are model that electrons in the of number thatat any given atom shells of valence the ing from the num- instant. By subtracting this average partialthe charge ber of protons in the molecule, is determined. atom each of Visualizing the partial charge of the atoms in a to understand the model's molecule is another way the greater the partial charge on Typically reactivity. it is to formlikely more the with bonds an atom, partialwhose atomsother charge is the opposite sign. , and . Surface looking at the mapped hydrogen. This small hydrogen. . ation of unpaired spination of unpaired Surfaces>Display Mode>Wire Mesh Surfaces>Display Mode>Wire Total Spin Density Total select 3.Isospin to 0.001. Set 2. Go to Tutorial 10: Partial Charges 10: Partial Tutorial of a molecule contributes an integralatom Each This integralas a whole. charge to the molecule formalthe as contribution is known charge of the atom. the compute the integral of a molecule, charge To its of each contributed by of electrons number of pro- atoms can be subtracted from the number of its atoms. of each tons in the nucleus There is a large concentr that it is, show but the calculations earlier, display in fact, there. over each of the terminaleach small con- and a carbons over the central centration over amount of spin density is not very significant—you when see it even could not Figure 2.38: Wire mesh surfaces mesh Wire 2.38: Figure Spin Density determinenot Here we alone, spin density the raw onto the chargesurface. densitymapped 1. point On theto toolbar, Surfaces of the radical—there is some radical character is radical—there of the some radical character theseboth onsimultaneously carbons. of toggle the Surfaces clicking the surface off by Now, icon. 42

Administrator 1. Go to the File>New. 5. In the min/max text boxes, select the range of 2. Using the Text Building tool, click in the model calculations you want to colorize. To select the window. entire range of values calculated for the model, click the Scan Value Range button. 3. Type PhOH in the text box, and press the Enter key. A molecule of phenol is created. 6. To view the model with your options, select the Preview checkbox at the bottom of the dialog 4. To compute Extended Hückel charges, go to box and click Apply. Calculations> Extended Hückel>Calculate Charges. 7. Click OK when finished. The Atom Property table opens, displaying the results. To view the table at any time, go to All the atoms are colored according to the color View>Atom Property Table. scale you chose. Atoms with a large negative partial charge are deep blue. Atoms with a large positive Displaying Partial Charges partial charge are deep red. As the magnitude of the charges approaches 0, the color of the atom You can use varying gradients of color to illustrate becomes paler. partial charges for atoms in your model. For example, strongly positive charged atoms may appear Figure 2.39: Partial charges for phenol bright red while strongly negative atoms appear blue. Lesser positively and negatively charged atoms also appear somewhere within the color range, depending on the value. To display partial charges, you first need to run the charge calculation. To display partial charges: 1. Go to File>Model Settings and select the Colors & Fonts tab. 2. Under Color by, select Atom Properties. For phenol, the greatest negative charge is on the 3. In the Atom Properties drop-down list, select oxygen atom. The greatest positive charge is on the Charge(Hückel). adjacent carbon atom (with the adjacent hydrogen 4. Select one of the two color bands. The first band atom a close second). The rest of the molecule has ranges from blue to red. The second band has a relatively pale atoms; their partial charges are much more refined range of color. closer to zero.

Chem & Bio 3D 11.0 43 User Guide Chapter 2 Chapter 44

Administrator Chapter 3: Displaying Models

You can display molecular models in several ways, To change the structural display type of a model depending on what information you want to learn temporarily, click the arrow on the Model Display from them. The atoms and bonds of a model can tool and select the display type. take on different appearances. In Chem & Bio 3D 11.0, an appearance is called a model display (also Structure Display Modes called a rendering type). Depending on the type of The following table describes the Chem & Bio 3D molecule, certain model displays may offer advan- 11.0 modes for structure displays: tages by highlighting structural features of interest. For example, the Ribbons model display might be the option of choice to show the conformational Display Mode Description folding of a protein without the distracting structural detail of individual atoms. Wire Frame Wire frame models are Model display options are divided into two general the most simple display types, structure displays and molecular surface dis- mode. Bonds are displays. played as pixel-wide lines. Atoms are not dis- Structure Displays played explicitly, but each half of a bond is colored Structures are graphical representations based on to represent the element the traditional, physical three-dimensional molecu- color for the atom. Wire lar model types. The following structure display frame models are well types are available from Model Display view of the suited for extremely large Chem & Bio 3D 11.0 Setting dialog box: models such as proteins. •Wire Frame Sticks Stick models are similar •Sticks to wire frame, however, • Ball and Stick the bonds are slightly • Cylindrical Bonds thicker. This model type is also good for visualiz- • Space Filling ing very large models • Ribbons such as proteins. • Cartoons To change the default structural display type of a model: 1. Go to File>Model Settings. The Model Settings dialog box appears. 2. Select the Model Display tab. 3. Set the new options.

Chem & Bio 3D 45 User Guide Show Show Chapter 3 Chapter . section, click the section, click tab. These models show largeThese models show protein in a molecules formhighlight sec- that ondary tertiary and structure. Ribbon models can be groupcolored by to acid identify the amino model Your constituents. a protein have must rib- to display backbone bons. rib- like Cartoonmodels, large show models, bon protein molecules in a formhighlights sec- that ondary and tertiary structure. Ribbon and Cartoon do modes display model not provide pop-up information and are not as intended for printing bitmaps. Settings

Atom & Bond . File>Model Atom Dot Surfaces Click OK By Default checkbox. Display ModeRibbons Description Cartoons 3. In the Displaying Solid Spheres and space filling cylindrical bonds, In ball and stick, repre- the solid spheres display can you models, control their size in individual and senting atoms atoms or all atoms. default on all atoms: solid spheres by display To 1. Go to 4. 2. Select the These show models lines and bonds as thick filled spheres. atoms as The spheres atom are filledwith color thatcor- responds to the element or positionatom.the of These models are similar to Ball and Stick that all models except as bond types are drawn cylinders. These models are best the elec- for displaying among clouds tron These models atoms. to draw be complex may display. to slow and are scaled to Atoms der van 100% of the in radii specified Waals table. Types the Atom radii Waals der The van be set so overlap may non-bondedbetween atoms indicates a large (about 0.5 kcal/mole) interaction. repulsive Ball and Stick Ball Bonds Cylindrical Space Filling Display Mode Description 46

Administrator 5. Go to View>Model Display and select or deselect Figure 3.1: Viewing dot surfaces Show Atom Dots. Setting Solid Sphere Size The maximum radius of the sphere that represents an atom can be based on the van der Waals radius or partial charge. To specify which property to use, select the radio button below the slider. The van der Waals radius is specified using the atom type of the atom. The partial charge is the result of a calculation: Extended Hückel, MOPAC, or Gaussian. If you have not performed a calculation, the partial charge for each atom is shown as 0, and the model The dot surface is based on the van der Waals will display as a stick model. radius or partial charges as set in the Atom Display When sizing by partial charge, the absolute value of table of the Model Settings dialog box. the charge is used. An atom with a partial charge of To display dot surfaces by default on all atoms: 0.500 will have the same radius as an atom with a 1. Go to File>Model Settings and select the Atom & partial charge of -0.500. Bond tab. Atom Spheres Size% 2. In the Atom Dot Surfaces section, click the Show The value of the Atom Sphere Size% slider on the By Default checkbox. Atom & Bond tab represents a percentage of the 3. Use the Density slider to adjust the density of the Covalent radius specified for each atom in the Ele- dot surface and click apply. ments Table. This percentage ranges from 0 (small) 4. Click OK when finished. to 100 (large). Thus, when the Atom Size is 100, All atoms currently in the model window display the atoms are scaled to their maximum radii. The the selected option. value of this setting affects Ball and Stick and Cylindrical Bond models. To toggle the display of dot surfaces in a model, go to View>Model Display>Show Atom Dots. Displaying Dot Surfaces Coloring Displays You can add dot surfaces to any of the model display types like the stick model shown below. You can change the default for the way colors are used to display your model in the Model Display tab of the Model Settings control panel. To make a temporary change, Go to View>Model Display> Color By and select a menu option. The options are: • Monochrome • Partial Charge •Chain •Element

Chem & Bio 3D 47 User Guide and Chapter 3 Chapter

icon on Stereo & Stereo tab . View>Model View>Model Depth fading . and select the slider to adjust the Red & Blue or click the or click Eye Separation File>Model Settings File>Model Render Red/Blue Anaglyphs Anaglyphs Red/Blue Render tab. and choose and choose File>Model Settings>Stereo & Depth Depth Fading Depth Fading effect. Depth To toggle go off, the effect on or to To the Model Display Toolbar: Toolbar: the Model Display . Red-blue Anaglyphs Chem & Bio 3D 11.0 supports viewing with red- effect. a stereo create to glasses blue 3D Toactivate red-blue viewing:1. Go to Depth Fading3D enhancement The depth11.0 fadingfeature in Chem & Bio 3D making partscreates a realistic depthby of effect fade into the furtherviewer the model the from depth shading, select the activate background. To to go Figure 3.2: Color by partial charge Color by partial charge 3.2: Figure 3. the Move Display 2. Select select As the partialAs the charge gets is 0, the atom closer to with a 0 partial Atoms charge are white. paler. The partial charge result of a calculation— is the If you or Gaussian. MOPAC, Hückel, Extended not performed have a calculation, the partial is 0. atom charge for each . TheEle- . . OK OK . The Color dialog The dialog . Color Tables>Elements field for an element. Thefield for an element. , right-click on the group, right-click Select Color Color Model Explorer View> Parameter Parameter View> You must save must effect. the changes before they take You Monochrome areand Chain only for available ments Table opens. ments Table Colorappears. dialog box box appears. box name and choose name and choose •Group •Depth 2. the Double-click 3. Select the color to use and click 2. Select the color to use and click Coloring by Partial Charge with a atoms partial When coloring by charge, partialnegative highly charge Atoms are deep blue. partial chargewithhighly positive are deep a red. Coloring by Group colors to groupsdifferent can assign (sub- You structures) in the model. associatedgroupchange a color with a in the To model: active 1. In the NOTE: Coloring by Element mode for small element is the default by Color Thedefault colors are stored in the Ele- molecules. ments Table. color of elements specified in the change the To Elements table: 1. Go to NOTE: proteins or Cartoon displayRibbon displayed the in mode. 4. the table. Close and save 48

Administrator Perspective Rendering 1. Go to File>Model Settings and select the Back- Chem & Bio 3D 11.0 supports true perspective ground tab. rendering of models. This results in a more realistic 2. Select the background color from the dropdown depiction of the model, with bond lengths and list and click OK. atom sizes further from the viewer being scaled To return to the default background color: consistently. The “field of view” slider adjusts the perspective effect. Moving the slider to the right 1. Go to File>Model Settings and select the Back- increases the effect. ground tab. 2. Click the Reset to Default button and click OK. Figure 3.3: Depth fading settings

NOTE: The background colors are not saved in PostScript files or used when printing, except when you use the Ribbons display.

Depth Fading, Coloring Individual Atoms Perspective, & field of You can mark atoms individually using the Select view slider Color command in the Model Explorer.

To change an atom to a new solid color: 1. Go to View> Model Explorer and select in the Model Explorer the atom(s) to change. 2. Right-click the atoms you selected and choose Select Color in the context menu. The Color dialog box appears. 3. Select a color and Click OK. The color of the atom(s) changes to the new color. NOTE: Moving the slider all the way to the left may make To remove a custom atom color from the model the model disappear completely. display: 1. In the Model Explorer, select the atoms whose Coloring the Background Window colors you want to change. 2. Right-click the atoms you selected and go to You can also select a background color. A black or Apply Atom Color>Inherit Atom Color. dark blue background can be particularly striking for ribbon displays intended for full color viewing, Lone Electron Pairs whereas a light background is more suitable for Some molecules, such as amines and carboxylic print copy. acids, have lone electron pairs that you can add or To change the background color of the model win- remove when modifying your model. After you dow: add an electron pair, you can show or hide the electrons without chemically changing your model.

Chem & Bio 3D 49 User Guide Chapter 3 Chapter . how Serial Num- Atom and choose either and choose and right-click the and right-click Show Serial Numbers. or View>Model Display View>Model View>Model Explorer View>Model Atom Serial Number>S Atom Symbol>Show Atom Symbol Atom Symbol>Show or icon Toolbar. the Model Display on Show Atom Symbols Show Atom atom(s). Explorer isn’t open already. Explorer isn’t group in the list. the desired option.choose ber •Go to to •Go • the Atom Label Click Numbers or Serial 2. Go to To toggle at or Serial Numbers Labels the Atom To the following: of do one any time, Displaying Group Labels Displaying Group A group modelthat is a selectionatoms of in your decide to groupmay you example, For define. you togethera particular all the atoms in or other chain can then name the group structural You feature. allthe the group atoms in the give want, and, if you proteins, as largesuch molecules For color. same organizeto decide atoms listed in the may you granular con- more A groups. into Explorer Model with the Group Labels command is available trol Model Explorer. in the on the context menus set group labels: To 1. the Model Go to View>Model Explorer if 2.of the one right-click In the Model Explorer, 3. Labels and select Group menu, In the context Displaying Labels Atom by Atom Displaying Labels in or serial numbers symbols element display To atoms: individual 1. Go to and Add tab submenu submenu Structure>Lone Structure>Lone Atom Labels . . and select either and select Model Display Model . tab select the font, point button. All atoms cur- button. Show or Hide Remove. Hide. Set as Default menu. or Structure>Lone Pair Structure>Lone Lone Display>Show Pairs View>Model Colors & Fonts Colors & Fonts File>Model Settings View and select and select & Show select either rently in the model window display the selected display rently in the model window options. size, and color. size, •Go to to •Go •Go to to •Go Setting Default Options and Serial Numbers set the Element Symbols To defaults: 1. Go to You can control the appearance of element sym- element can control the appearance of You using the numbers serial bols and 3. the Click Displaying Atom Labels Show/Hide Lone Pairs Show/Hide Lone whether or Hide options to specify Show Use the Keep in electron pairs mind are displayed. that hid- still partden electron pairs are model. the of ofone do the follow- or Hide Lone Pairs, Show To ing: Structure>Lone Pair>Add & Show Pair>Add Structure>Lone Lone Pairs Removing goto pair, electron an remove To Adding Lone Pairs Lone Adding go model, lone electronadd a pair to your to To Pair in the Model Settings controlin the Model Settingscorre-the panel, and sponding commands in the of the 2. On the 50

Administrator Figure 3.4: Residue labels Figure 3.6: Measurement display

Displaying Measurements Using Stereo Pairs The Measurement Table can display bond lengths and bond angles for your model. However, to view Stereo Pairs is a display enhancement technique these values, you must first generate them. Go to based on the optical principles of the stereoscope (a device for viewing photographs in three dimen- Structure>Measurements and select the measurements you want to generate. Afterward, go to sions). By displaying two images with a slight displacement, a 3D effect is created. View> Measurement Table. By default, a measurement will display if you add a single measurement Stereo views can be either parallel or reverse (direct but not if you generate a set of measurements. You or cross-eyed). Some people find it easier to look can choose which measurements to display by directly, others can cross their eyes and focus on expanding the Measurements Window to show the two images, creating an enhanced three dimen- Display checkboxes. sional effect. In either case, the effect may be easier Figure 3.5: Measurements window to achieve on a printed stereo view of your model than on the screen. Keep the images relatively small, and adjust the distance from your eyes. To set the Stereo Pairs parameters: 1. Go to File>Model Settings and click the Stereo & Depth tab. The stereo views control panel appears. 2. Select Render Stereo Pairs to display two views of the model next to each other. The right view is the same as the left view, rotated about the Y- axis. 3. Specify the Eye Separation (Stereo Offset) with the slider. This controls the amount of Y-axis rotation.

Chem & Bio 3D 51 User Guide Chapter 3 Chapter Stereo & Stereo sub- Solvent Solvent , adjust the Eye Sep-, adjust the Choose Surface and select the and select when finished. command on the command on General Stereo Settings Stereo General File>Model Explorer File>Model OK tab. Depth aration slider. 3. Click Accessible Extended Hückel semi-empirical method you a is Extended Hückel for generate rapidly to surfaces molecular can use pro- this reason, we For most molecular models. to performa brief discussion on how vide an calculation. Extended Hückel Controlling Separation Controlling adjusting the stereo can adjust the by effect You eye separation. 1. to Go Molecular Surfaces information provide Molecular surface displays toopposed the atom as molecules, about entire and bond information structure by provided dis- informationSurfaces show about a mole- plays. They properties. and chemical physical cule’s aspects the externalof display surface interface or of a molecule. distribution electron the can be displayed, molecular surface any Before necessary be cal- data describe the surface must to of the or one culated using Extended Hückel or Gaussian. in CS MOPAC methods available Sur- Molecular choose must you (Under MOPAC propertiesthe faces as one of to be calculated.) that you to the requirement There is one exception performmust calculationmolecular before a sur- a surfaces accessible Solvent face can be displayed. are automatically calculated from parameters addi- Therefore, no stored in the parameters tables. the are needed, and calculations tional menu is always active. is always menu 2. Under Separa- . and select the OpenGL to rotate the right frame to the to the right frame to rotate to rotate the right view further to rotate the to whenfinished. Reversed Parallel File>Preferences You must enable “stereo in OpenGL” in the dis- in the “stereo enable must OpenGL” in You Use Hardware Stereo when Available when Use Hardware Stereo OK slider. About 5% of the width is a typical is a the width 5% of About slider. the right. left. If your left eye focuses on left. If the your right-hand on the right eye focuses model and your can over- stereo views two left-hand model, the lap. separation for stereo viewing. separation viewing. stereo for tion tab. • Select • Select To select whether the views are cross-eyed or cross-eyed the views are select whether To of the following: one direct, do 2. Select NOTE: you areusing. with can use depthperspective fading and You not activate enhancement, but should hardware other stereo modes. Chem & Bio 3D 11.0 provides stereo graphics stereo 11.0 provides Chem & Bio 3D rendering forthat hashardware stereo OpenGL capa- of stereo There graphics are a variety cards, bilities. available. and 3D monitors stereo glasses, 1. Go to Stereo Enhancement Stereo 4. the degree Specify of separationusing the 3. Click is enabled, stereo enhancement the hardware Once window. in any 3D available is play adapter properties control, as wellin Chem3D pref- as and select the correcterences, mode for the glasses/monitor 52

Administrator To compute molecular surfaces using the Different calculation types can provide different Extended Hückel method, go to Calcula- results. If you have performed more than one cal- tions>Extended Hückel>Calculate Surfaces. culation on a model, for example, both an Extended Hückel and an AM1 calculation, you must choose which calculation to use when gener- NOTE: Before performing an Extended Hückel calcula- ating the surface. tion, Chem & Bio 3D 11.0 deletes all lone pairs and dummy atoms. 1. Go to Surfaces>Choose Calculation Result and select one of your calculations. 2. Go to Surfaces>Choose Surface and choose a sur- At this point, a calculation has been performed and face types. the results of the calculation are stored with the model. To compute partial charges using the Extended NOTE: The Choose Surface commands are toggle Hückel method, go to Calculations>Extended switches–click once to display, click again to turn off the dis- Hückel>Calculate Charges. play. You can display more than one surface at a time. When a surface is displayed, its icon is highlighted. For each atom in the model, a message is created listing the atom and its partial charge. If you have selected Partial Charge in the Pop-up Information tab 3. Adjust the display using the surface display tools. of the Model Settings dialog box, then the partial charges will appear as part of the pop-up information when you point to an atom. TIP: If you make a lot of adjustments to the display, activate the Surfaces toolbar and tear off the specific tools you will Displaying Molecular Surfaces be using often. To display a surface: 1. Decide what surface type to display. For a description of the surface display tools, see 2. Perform a suitable calculation using Extended “The Surfaces Toolbar” on page 15. Hückel, CS MOPAC, or Gaussian 03. Include Not all surfaces can be displayed from all calcula- the Molecular Surfaces property calculation when- tions. For example, a Molecular Electrostatic ever it is available. Potential surface may be displayed only following a Gaussian or MOPAC calculation. If a surface is unavailable, the command is grayed out in the sub- NOTE: CS MOPAC and Gaussian 03 surfaces calcula- menu. tions are only available in ChemBio3D Ultra 11.0. To generate surfaces from MOPAC or Gaussian, you must choose Molecular Surfaces as one of the properties calculated by these programs. The sur-

Chem & Bio 3D 53 User Guide Chapter 3 Chapter MOPAC Gaussian Theis dis- surface as an opaque played form.goodSolid is a are when you choice interested in the details itself, of the surface and not particularly interested in the under- lyingatoms and bonds. Theis dis- surface as a connected played WireMesh net of lines. goodis a when choice to focus on want you but surface features, of some idea still want the atoms and bonds in the structure. ent types of surface dis- types ent No YesYes Yes Yes Yes Extended Extended Hückel the parameters tables. This surface is always available with no further calculation. Calculated automatically from parameters stored in a. Surface TypeSolid Description Wire Mesh Surface Surface Type Molecular Electro- static Poten- tial Molecular Orbitals Setting Molecular Surface Types Surface Molecular Setting Chem3D offers fourdiffer These properties. types are with its own each plays, table: in the following shown MOPAC Gaussian NAYes NAYes NA Yes YesYes Yes Yes YesNo Yes YesYes Yes No Yes Yes Yes No Yes Yes Yes Extended Hückel a Spin Density map requires that MOPAC or Spin Density map requiresthat MOPAC Surface Type Solvent Accessible Connolly Molecular Total Charge Density with Molec- ular Orbital map with Spin Density map with Partial Charges with Molec- ular Electro- static Potential map Total Spin Density NOTE: wavefunction. face and types necessarythe calculations to display table. following the in are summarized them Gaussian computations be performed with an open shell 54

Administrator To set an isovalue: Surface Type Description 1. Go to Surfaces>Choose Surface and select a sur- Dots The surface is dis- face type. played as a series of 2. On the Surfaces menu, select either Isocontour. or unconnected dots. Isocharge. Dots are a good choice 3. Adjust the slider to the new isovalue. if you are primarily The new isovalue is the middle value listed at the interested in the under- bottom of the Isocontour tool. lying structure and just want to get an idea of Setting the Surface Resolution the surface shape. The Surface Resolution is a measure of how Translucent The surface is dis- smooth the surface appears. The higher the resolu- played in solid form, tion, the more points are used to calculate the sur- but is partially trans- face, and the smoother the surface appears. parent so you can also However, high resolution values can also take a see the atoms and long time to calculate. The default setting of 30 is a bonds within it. Trans- good compromise between speed and smoothness. lucent is a good com- To set the resolution: promise between surface display styles. 1. Go to Surfaces>Resolution. The Resolution slider appears. Setting Molecular Surface Isovalues 2. Adjust the slider to the desired resolution. Isovalues are constant values used to generate a The new resolution is the middle value listed at the surface. For each surface property, values can be bottom of the Resolution tool. calculated throughout space. For example, the elec- Setting Molecular Surface Colors trostatic potential is very high near each atom of a molecule, and vanishes as you move away from it. How you set the color depends on what type of Chem3D generates a surface by connecting all the surface you use. points in space that have the same value, the isov- For Solvent Accessible, Connolly Molecular, or alue. Weather maps offer other common examples Total Charge Density surfaces, do the following: of isovalues in two dimensions, connecting loca- 1. Go to Surfaces>Color Mapping>Surface Color. The tions of equal temperature (isotherms) or equal Surface Color dialog box appears. pressure (isobars). There are two isovalues to select 2. Select the new color. from, depending on the surface you choose. For the total charge density surface, set the isocharge For Total Spin Density, Molecular Electrostatic value; for the molecular orbital surface, se the isoc- Potential, and Molecular Orbital surface types, you ontour value. must specify two colors. On the Surfaces menu, choose Color A or Color B.

Chem & Bio 3D 55 User Guide

. Chapter 3 Chapter 1 . plorer when creating plorer when ne proteins”, Annu. Annu. ne proteins”, Electrostatic Potential the Advanced Molecular Molecular the Advanced and is displayed according to a according is displayed is based on the default colors on the defaultis based is based on the colors (if any) you any) you (if colors the is based on is based on the displayed atom atom on the displayed based is Surfaces>Choose Result Surfaces>Advanced Molecular Surfaces Molecular Surfaces>Advanced tifying nonpolar transbilayer helices in amino amino helices in transbilayer nonpolar tifying membra of acid sequences Biophys. Biophys.Rev. Chem.321-353, 15, 1986. Partial Surfaces Partial Scientists who study protein-ligand interac- Partial Charges 1. Engelman, D.M.; Steitz, T.A.; Goldman, A., “Iden- 1. Engelman, D.M.; T.A.; Steitz, Atom Color Atom ele- be the default not may or may (these colors ment colors). Color Element Table. in the Elements Color Group the Model Ex specified in groups. Hydrophobicity from derived convention widely-used color the most where hydrophobicities, amino acid (lipophilic)is least red and the hydrophobic (lipophobic) is blue. hydrophobic include and exclude in and exclude include Surfaces dialog box. • • • • tions are often interested in generatingin tions are often interested a molecular a ligand.does not include that protein surface of a 11.0 can Ultra ChemBio3D Ultra 11.0 and Bio3D and Connolly Accessible generate partialSolvent exclud- or by ligands, excluding either by surfaces, partsselected or both. ing of the model, generate a partial surface: To 1. Go to (derived from the partial charges) properties(derived are currentlythe from calculation. If taken selected performedhave one more than calculationyou on to calculation which can specify the model, you Go to use. The The 2. to want type and what you Select the surface be default but may by atoms are excluded Solvent atoms (usually Hidden with the checkbox. included or excluded. also be included may hydrogens) slider Radius . The the solvent-accessible the solvent-accessible provides color-coded rep- color-coded provides

colors, groups of atoms, groups of atoms, colors,

is the color you have chosen for chosen have is the color you Surfaces>Solvent Radius Surface Color the molecular surface. the molecular surface. appears. • WaterMethanolEthanol 1.4 1.9 Acetonitrile 2.2 2.3 AcetoneEther 2.4 Pyridine 2.4 DMSO 2.4 Benzene 2.5 Chloroform 2.6 2.7 Solvent (Å) Radius 2.slider to the desired resolution. Adjust the listed at the Thevalue the middle new radius is tool. of the Radius bottom The Mapping PropertyThe Mapping Setting Surface Mapping To set the solvent radius: set the solvent To 1. Go to Setting Solvent Radius Solvent Setting The slider. using the radius solvent set the can You for radius water. 1.4 Å, is the value default solvent below: are shown solvents some common Radii for hydrophobicity, partial charges, and electrostatic and partial charges, hydrophobicity, potential superimposed on surface. resentations of atom 56

Administrator Figure 3.7: Partial surface excluding solvent atoms defined as the locus described by the center of the probe sphere, as shown in the diagram below. Figure 3.9: van der Waals surfaces Solvent accessible surface van der Waals surface

Solvent probe After displaying a surface, you can set surface transparency and reflectivity. You can color the surface by atom, element, or group color, or by group hydrophobicity, in addition to monochro- matic surfaces of any color. You can also restrict the surface either by distance from the selected group, or by flooding. Figure 3.8: Restricted surface with ligand excluded Connolly Molecular Surface The Connolly surface, also called the molecular surface, is similar to the solvent-accessible surface. Using a small spherical probe to simulate a solvent, it is defined as the surface made by the center of the solvent sphere as it contacts the van der Waals surface. The volume enclosed by the Connolly surface is called the solvent-excluded volume. These surfaces are shown in Figure 3.10. Figure 3.10: Connolly or solvent-excluded surface

Solvent-Accessible Surface The solvent-accessible surface represents the portion of the molecule that solvent molecules can access. To determine the solvent-accessible surface, a small probe sphere simulating the solvent molecule is rolled over the surface of the molecule (van der The Connolly Surface of icrn is shown in Figure Waals surface). The solvent-accessible surface is 3.11.

Chem & Bio 3D 57 User Guide Chapter 3 Chapter ion is indicated by posi-ion is indicated by gions of the total spin of the total gions er orbital theory, the theory, er orbital MOPAC or Gaussian using MOPAC MEP Therepre-(MEP) molecular electrostatic potential a mole- sents the attraction or repulsionbetween and a proton.cule is represented Attraction by negativevalues and repuls tivevalues. Experimental MEPvalues can be diffrac- diffraction or electron X-ray obtained by insight into which and provide techniques, tion regions of a molecule are more susceptible to elec- can visualize You attack. trophilic or nucleophilic is color when MEP by values MEP the relative mapped onto another surface (totalchargeden- most the red, is value MEP sity). Themost positive and neutral is white. blue, negative Molecular Orbitals represent surfaces visually Molecular orbital (MO) of stable electron distributions a mole- the various According to fronti cule. symmetries of the highest-occupied shapes and Total Spin Density Spin Total the differ- The describes surface spin density total spin-down spin-up and ence in densities between space. a molecule’s region of in electrons given any region, the The largera given in the difference elec- an unpaired more thatregion approximates or of spin-up predominance tron. The relative electrons in re spin-down color when surface can be visualized by density mapped ontosurface density is total spin another (total charge(positive density). Entirely spin-up (nega- spin-down red, entirely electrons are value) electrons and paired (neutral) are white. blue, tive) to exam- surface use the total spin density can You Thesur- molecule. of a ine the unpaired electrons are unpaired electrons face exists only where density surface total spin the present. Viewing requires that both spin density and molecular surfaces are calculated by an open shell wavefunction. Ultra only Ultra Ultra only menu. menu. Surfaces to map onto the surface map onto the to

tool on thetool on for the highest magnitude submenu. Molecular Orbital Orbital Molecular HOMO/LUMO Thein appears in parentheses the orbital number The total charge density is the electron density in Theelectron density the total charge density is or a molecule, of the space surroundingnuclei the electrons in the for finding the probability function The default isocharge molecule. a space around This of 0.002 atomic units (a.u.). value value radius Waals der van the molecule’s approximates representsentire three- and the of about 95% the molecule. dimensional space occupied by visible best Thethe is total charge surface density as deter- shape, representationmolecule’s of a its electronic distribution. Themined by total is calculated from scratch charge density surface generallyis molecule and more accurate for each than the space filling display. propertiesthe total charge surfaces, density For are molecular orbital, spin mapping for available electrostatic potential, and partialcharges. density, The color scale uses red magnitude of the property. and blue for the lowest white. Neutral is orbital the choose can You Total Charge Density Total with the Figure 3.11: Connolly icrn surface of Connolly 3.11: Figure 58

Administrator Ultra only and lowest-unoccupied molecular orbitals (HOMO not specified an isocontour value, the default value and LUMO) are crucial in predicting the reactivity is 0.01. of a species and the stereochemical and regiochem- ical outcome of a chemical reaction. Other Sources Go to Surfaces>Select Molecular Orbital to see the list You can use files from sources other than Chem & of HOMO/LUMO orbitals in the model. Select Bio 3D 11.0 to visualize surfaces. From Windows the orbital you want to view. sources, you can open a Gaussian Formatted You can specify the isocontour value for any com- Checkpoint (.fchk) or Cube (.cub) file. puted MO surface using the Isocontour tool on the From sources other than Windows, create a Gauss- Surfaces menu. The default isocontour value for a ian Cube file and open it in Chem & Bio 3D 11.0. newly computed surface is the value you last specified for a previously computed surface. If you have

Chem & Bio 3D 59 User Guide Chapter 3 Chapter 60

Administrator Chapter 4: Building and Modifying Models

Chem & Bio 3D 11.0 enables you to build or using the Structure menu Rectify and Clean Up change a model by three principal methods: tools. • Using the ChemDraw panel, which uses Chem- To change the building mode: Draw to build and insert or copy and modify 1. Go to File>Model Settings. The Model Settings models. dialog box appears. • Using Bond tools, in which build a hydrocar- 2. Select the Model Building tab. bon structure and modify bonds and atoms as Figure 4.1: The Model Building controls needed. • Using the Build from Text tool (hereafter referred to as the Text tool), which allows you to build or modify models using atom labels and substructures. Usually, a combination of these methods yields the best results. For example, you might build a carbon skeleton of a model with ChemDraw or the bond tools, then change some of the carbons into other elements with the Text tool. Or you can build a model exclusively using the Text tool. In addition, you can use Structure tools to change bond lengths and angles, or change stereochemistry. Setting the Model Building Controls You control how you build by changing options in the Model Building tab in the Model Settings dialog box. The default mode is all options selected. 3. Select or deselect the appropriate radio buttons, You can choose to build in a faster mode, with less described below. built-in “chemical intelligence”, by turning off one Correct Atom Types. Determines whether atom or more of the options. types are assigned to each atom as you build. Atom Intelligent mode yields a reasonable 3D model as types, such as “C Alkane” specify the valence, you build. Alternatively, fast mode provides a quick bond lengths, bond angles, and geometry for the way to generate a backbone structure. You can atom. then turn it into a chemically reasonable 3D model Rectify. Determines whether the open valences for an atom are filled, usually with hydrogen atoms.

Chem & Bio 3D 61 User Guide Chapter 4 ink Mode ink Mode changes the other auto-changes You can also paste chemical formulas the into You structure,the click icon. •replace with the ChemDraw the model To • simply add the structure click To . Chem3D Model window. Be aware, however,Be aware, a formula that window. Chem3D Model button at the top left of the ChemDraw panel. at thebuttonChemDraw the top left of syn- can still manually you dualoff, link with Even Panel. and ChemDraw window Model the chronize Copy either the Add or icons. Click Name=Struct you The Name=Structallows ChemDraw window name or a enteringa chemical by models to build can also copy names or You SMILES string. and paste other documents strings from SMILES or them, either into the Name=Struct window, directly into the Model window. TIP: may represent an isomer. Building with Other 2D Programs as packages such use other 2D drawing can You structures, then to create chemical ISIS/Draw automatic conversion copy them into Chem3D for to a 3D model. Drawing small molecules small Drawing can begin you is active, panel the ChemDraw Once a structure, you have Once you structures. drawing window. to the Model it can display Unlink Mode in dual link works panel default, the ChemDraw By model appears simulta- your mode, In this mode. Chem3D. in panel and neously in the ChemDraw modifying either model matically. Unl the turn click mode, off dual link To Determines Determines By default, the When selected, all Determines the whether For more informationstandard about atom types, For View>ChemDraw Panel. View>ChemDraw If you don’t see the Tools palette, right-click in the in right-click palette, see the Tools don’t you If 62 ChemDraw panel to the right appears the of ChemDraw model window. appears. 2. palette it. TheTools panel to activate thein Click TIP: ChemDraw panel,select and View>Show Main Toolbar. Building with the ChemDraw Panel or to create it easy 11.0 makes Chem & Bio 3D modify models in ChemDraw. panel: open the ChemDraw To 1. Go to NOTE: Basics” on page 17. entire model is resized and centered in the model in the model and centered resized is entire model a change the model is made. to after window System. Detect Conjugated conjugatedbonds in a set at a bond are system order of 1.5. When bonds are displayed unselected, struc- drawn Does not affect previously drawn. as tures. (%). Addition Bond Proximate Apply Standard Measurements. Measurements. Apply Standard associated measurements the standard whether build. withapplied as you an atom type are Fit Model to Window. selection of a createdwhether between a bond is more information For see “Bonding by atoms. on pageProximity” 71. measurements, and rectification, see “Model Building

Administrator To build a model with 2D drawings: 3. Release the mouse button to complete the bond. 1. In the source program, copy the structure to the 4. To add bonds to the model, click and drag from clipboard. an atom you just drew. 2. In Chem3D, go to Edit>Paste. After you have the basic structure, you can change The 2D structure is converted to a 3D model in the carbons to different heteroatoms. Chem & Bio 3D 11.0. Rectification The standard measurements are applied to the When Correct Atom Types and Rectify settings are structure. For more information see “Appendix D: selected in the Model Building tab panel 2D to 3D Conversion.” (File>Model Settings>Model Building tab), the atom type is set according to the bond tool used NOTE: You cannot paste from ISIS/Draw into the (C Alkane in this example) and the appropriate ChemDraw panel, only into the Model window. You can, number of hydrogens are added. however use the synchronize control to add the model to the When the Rectify option is set in the Model Build- ChemDraw panel. ing tab, the hydrogen is replaced by a carbon. Adjusting Bond Width You can also cut-and-paste, or drag-and-drop, models to and from ChemDraw to Chem3D or the Typically, all the bonds in your model will look the ChemDraw panel. See “Copying to other applica- same and be a specified width. However, if you tions” on page 105 for more information. want, you can emphasize part of the structure or even just one bond by adjusting bond widths as Chem & Bio 3D ignores on-bond or atom objects desired. copied to the clipboard (arrows, orbitals, curves). Superatoms in ISIS/Draw are expanded if 1. Right-click the bond whose width you want to Chem3D finds a corresponding substructure. If a modify. corresponding structure is not found, you must 2. Choose Select Bond Size from the context win- define a substructure. For more information, see dow. “Defining Substructures” on page 157. 3. In the Bond Size Selection dialog box, use the slider to modify the width. Building With the Bond Tools Adjusting all bonds Use the bond tools to create the basic structure of your models. After you draw a bond, you can mod- To adjust the width for all bonds in your model: ify it to look the way you want. For example, you 1. Go to File>Model Settings and select the Atom & can change the carbons or hydrogens to other ele- Bond tab. ments or hide the hydrogens to reduce clutter on 2. Move the Bond Size slider to the desired width. the screen. 3. Click OK when finished. To create a model using a bond tool: Undefined Bonds and Atoms 1. Choose a bond tool. The Single Bond tool is used in this example. Use the Uncoordinated Bond tool to create 2. In the Model window, click and drag in the direc- an uncoordinated bond with a dummy atom tion you want the bond to be oriented. (labeled Du). Uncoordinated Bonds and dummy

Chem & Bio 3D 63 User Guide

Chapter 4 tab and and tab Delocalized Bonds Show Delocalized Bonds as Show Delocalized and benzene, shown below. shown benzene, and - 2 to remove only that bond. only that remove to

check box. View>Model Display> View>Model File>Model Settings>Model Display Settings>Model File>Model or bond. attached bonds. bonds. attached and select an option. and select (or deselect) the Dashed Lines • the Eraser tool Click the atom and click •bond a Click •Go to • to CTRL-k. Type •Go •atomand all the an atom to remove Click •Go to to •Go To remove an atom or bond, one of the follow- do remove To ing: Examples of Kekule and delocalized bonds. delocalized and Examples of Kekule Removing Bonds and Atoms and atoms: bonds remove When you After you build your model, you can togglemodel,build you your After you andofany the delocalized bonds Kekule between three ways: following their Kekule or delocalized form. Two typical form. delocalized or Kekule their Two are CO examples nglebonds in aromatics Dummy atom 64 Alternatingand si double Displaying Delocalized Bonds in and other either compounds can be displayed Figure 4.2 : Dummy atoms Figure atoms are ignored in all computations. An uncoor- computations. in all are ignored atoms a connection to specify you dinated bond allows without atoms strict definition a of two between bond. This the type of often in coor- used is bond forinorganic dination complexes compounds, be substituted. might element where another for positioning are also useful atoms Dummy atoms in a Z-matrix, perhaps for export to another This helpfulapplication is for further analysis. largewhen models become are and connectivities difficult to specify. atom: add an uncoordinated dummy bond and To 1. the Select Uncoordinated Bond tool. 2.atom. to an atom and drag from the Point An uncoordinated atom are bondadummy and Theadded to the model. labeled atom created is & Bio 3D 11.0 element symbol Chem the “Du”, atoms. for Dummy

Administrator • Select the atom or bond, and from the Edit • If you double click an atom, the contents of the menu, choose Clear. previous text box are applied to that atom. If • Select the atom or bond and press Delete. the atom is one of several selected atoms, then the contents of the previous text box are applied to all of the selected atoms. NOTE: If automatic rectification is on, you will not be able • If a tool other than the Text tool is selected, to delete hydrogen atoms. Turn rectification off when modify- double-clicking in the model window is equiva- ing a model. (Go to File>Model Settings>Model Building lent to clicking with the Text tool selected. Tri- tab.) ple-clicking in the model window is equivalent to double-clicking with the Text tool selected. The interpretation of the text in a text box depends Building With The Text Tool on whether atoms are selected as follows: The Text tool allows you to enter text that repre- • If the model window is empty, a model is built sents elements, atom types (elements with specific using the text. hybridization), substructures, formal charges, and • If you have one or more atoms selected, the serial numbers. The text you enter must be found text is added to the model at that selection if in either the Elements, Atom Types, or Substruc- possible. If the specifications for a selected tures tables. The match must be exact, including atom are violated, the connection cannot be correct capitalization. These tables can be found in made. the Parameter Tables list on the View menu. • If you have a model in the window, but do not have anything selected, a second fragment is NOTE: For all discussions below, all the Model Building added, but is not connected to the model. tab options in the Chem 3D Setting dialog box are assumed • When a text box is visible, you can modify the to be turned on. selection by Shift+clicking or Shift-dragging across atoms. Here are some general rules for using the Text Symbols and Formulae Tool: With the Text tool, you can create structures by • Text is case sensitive. For example, the correct entering chemical symbols and formulae, as way to specify a chlorine atom is Cl. The cor- described by the examples below: rect way to specify the phenyl group substructure is to type Ph. PH or ph will not be To use an element symbol in a text box: recognized. 1. Select the Text tool. •Pressing the Enter key applies the text to the 2. Click in the model window. A text box appears. model. 3. Type C. • Typing a formal charge directly after an ele- 4. Press the Enter key. A model of methane appears. ment symbol will set the formal charge for that The atom type is automatically assigned as a atom. For example PhO- will create a model of C Alkane, and the appropriate number of hydro- a phenoxide ion instead of phenol. gens are automatically added. To use the same text to add another methyl group:

Chem & Bio 3D 65 User Guide Chapter 4 key. A key. Enter into a text box . View>Parameter View>Parameter Edit>Paste . (CH3)3CNH2 (indicated by the amino acid name alone) and name the amino acid (indicated by a ß- preceding the name of by beta (indicated Thethe amino acid) forms. angles dihedral beenbuilding preset for alpha helix and have beta sheet forms. or atom types. elementswith single tion can use for table that you Groups the record in group. easy selection or coloring of groups, by ing polymers. atom (bonding atom) pre-configured. •substructures Acid Amino come in both alpha • can use substructures alone or in combina- You • Using a substructure automatically creates a • Substructuresparticularly are build- useful for • Substructures are energy minimized. • Substructuresthanmore one attachment have For example, the substructure example, Ph for the phenyl For group point. The has a single attachment substruc- group ture COO for the carboxyl has attachment points carbon at both theand the anioniccarboxyl Theseoxygen. for insertion provide of this group siteswithin a model. are Similar multi-bonding acid and other polymer units. for all amino defined with no atoms selected and press the the and press with no atoms selected Here are some advantages for using substructures: for Here are some advantages Specifying Order of Attachment Specifying and complex formssimple the In both using for of attach- can specify the order you tool, the Text repeating and paren-ment and numbers units by theses. type example, For Using Substructures can use pre-defined functional groups called You avail- view the substructures To to build models. able substructures, go to Tables>Substructures 5. goto Chem3D, In of tert-butylaminemodel appears. . . key. key. A model of ethylamine of ethylamine A model key. key. key. . . Enter Enter Enter Enter . Edit>Copy View>Parameter Tables>Chem 3D Building Tables>Chem View>Parameter C Alkene CH3CH2NH N 66 appears. Atom Types Atom are selected. example a hydrogen, and click. The text box The click. and text box a hydrogen, example label. the previous appears with the atom. 2.or building type in the table. element the Select 3. Go to 3. the Press 4. the Press 4. Chem3D Model in the Window. Double-click The Table Editor The Table box: text enter text in a to Editor use the Table To 1. Go to Changing building types to change the buildingtext type can use a box You to example, For bonding characteristics. and change an alkane to an alkene: change the building type of some atoms: To 1. appears. carbonA text box atom. a Click 2.carbon the other atom. atoms Shift-click Both 3. Type 3. the Press 1. to replace, in this want you atom to the Point 2. the Press Thechangedorderare building type and the bond You to reflectethyleneamine. model of the new this toatomsatthecan point display and bonds new information. To add a different element: add a different To 1. appearsatom. a hydrogen A text Click over box 2. Type A nitrogen to form is added ethylamine. in one step: build ethylamine To 1.appears. A text box window. in the model Click 2. Type

Administrator • You can define your own substructures and Figure 4.3 : Ethane model add them to the substructures table, or create additional tables. For more information, see “Defining Substructures” on page 157. Building with Substructures You must know where the attachment points are for each substructure to get meaningful structures using this method. Pre-defined substructures have attachment points as defined by standard chemistry conventions. For more information see “Attachment point rules” on page 157. To use a substructure as an independent fragment, make sure there are no atoms selected. To insert a substructure into a model, select the atoms that are bonded to the attachment points of the substructure. NOTE: When automatic rectification is on, the free valence To build a model using a substructure: in the ethyl group is filled with a hydrogen. If automatic rectification is off, you need to type EtH to get the same result. 1. Type the name of the substructure into a text For substructures with more than one atom with an open box (or copy and paste it from the Substructures valence, explicitly specify terminal atoms for each open table). valence. 2. Press the Enter key. The substructure appears in the model window. When you replace an atom or atoms with a sub- Example 2. Building a Model with a structure, the atoms that were bonded to the Substructure and Several Other Elements replaced atoms are bonded to the attachment To build a model with substructures and other ele- points of the substructure. The attachment points ments: left by the replaced atoms are also ordered by serial number. 1. Type PrNH2 into a text box with no atoms selected. Example 1. Building Ethane 2. Press the Enter key. A model of propylamine To build a model of ethane using a substructure: appears. 1. Type Et or EtH into a text box with no atoms The appropriate bonding site for the Pr substruc- selected. ture is used for bonding to the additional elements 2. Press the Enter key. A model of ethane appears. NH2.

Chem & Bio 3D 67 User Guide key. Chapter 4 Enter key. repeatedly. For example, example, For repeatedly. . Enter OH polypeptide model model OH polypeptide and press the and press in the text box and press the in the text box + - To better view the alphaview better helix formation,use the To HAla(Pro)10GlyOH The charge is applied to the nitrogen atom. Its added. atom is a hydrogen atom type changes and 4. the terminal Click oxygen. atom. oxygen the appears over A text box 5. Type Trackball Tool to reorient the model to an end-on view. For For to reorient to an end-on view. the model Tool Trackball Figure 4.5 : HAlaGlyPhe 4.5 Figure TIP: page 85. on moreTool” information see “Trackball change the polypeptide to a zwitterion: To 1.tool. Select the Text 2. the terminal Click nitrogen. nitrogenthe atom. appears over A text box 3. Type type The charge is applied to the oxygen atom. Its atom atom. Its oxygen Thethe to charge is applied removed. atom is type changes and a hydrogen amino acids that repeat, put parentheses For around the repeating rather a number unit plus than type the amino acid Hß–Alaß– character, type character, ß into a text box with no into a text box key. . To generate the generate . To Enter You can use the amino acid names preceded with a You HAlaGlyPheOH The additional H and OH cap the ends of the and OH cap the ends of H additional The ends cap theand polypeptide.you don’t If automaticrectificationto is on, Chem3D tries fillpossibly the openby valences, closing a ring. 68 to obtain the beta conformation, for example atoms selected. NOTE: ß– Alt+0223 using the number pad [Option+s. The appropriatebonding and dihedral angles for in the sub- amino acid are pre-configured each structure. 2. the Press Example 3. Polypeptides as such Use substructures building polymers, for proteins: 1. Type Figure 4.4 : Propylamine model Propylamine 4.4 : Figure Ring closing bonds the textappear in whenever a or more open valences. containstwo text box Theform alpha of neutral polypeptide the chain Phenylalanine and Glycine, of Alanine, composed appears. Glyß–PheOH

Administrator Example 4. Other Polymers Figure 4.7 : Changing a model with the text box Figure 4.6 The formation of a PET (polyethylene terephthalate) polymer with 4 units (a.k.a.: Dacron, Terylene, Mylar) ia shown below: PET model

To build this model, type OH(PET)4H into a text box with no atoms selected and press the Enter key. The H and OH are added to cap the ends of the polymer. 2. Type Ph. Replacing an Atom 3. Press the Enter key. Figure 4.8 : Biphenyl model The substructure you use must have the same number of attachment points as the atom you are replacing. For example, if you try to replace a carbon in the middle of a chain with an Ethyl substructure, an error occurs because the ethyl group has only one open valence and the selected carbon has two. To replace an individual atom with a substructure: 1. Click the Text tool. 2. Click the atom to replace. A text box appears. 3. Type the name of the substructure to add (case-sensitive). 4. Press the Enter key. The substructure replaces the selected atom. Building From Tables For example, to change benzene to biphenyl: Cartesian Coordinate tables and Z-Matrix tables 1. Click the atom to replace. A text box appears. can be saved as text files or in Excel worksheets. (See “Z-matrix” on page 19 and “Cartesian Coor- dinates” on page 19 for more information.) Like- wise, tables from text files or worksheets can be copied into blank tables in Chem3D to create models. Text tables can use spaces or tabs between columns. For a Cartesian table, there must be four columns (not including the Serial Number column) or five columns (if the Serial Number column is included.) The relative order of the X-Y-Z columns must be

Chem & Bio 3D 69 User Guide Chapter 4 changes with the text box the text with changes one element to another: one key. key. Enter Enter . NH2 sensitive). Figure 4.9 : Making multiple : Making 4.9 Figure 2. the Press ------as(tab separa-tableZ-Matrix 3: ethenolExample tor) C C11.33 O21.321119.73 180 H30.97821091 180 H20.9911193 180 H10.9892119.53 0 H10.98821193 Changing Elements change an atom from To 1.tool. the Text Click 2. appears. A text box the atom to change. Click 3. (case- the symbol for want element the you Type 4. the Press As long as the Text tool is selected, you can dou- selected, you is tool Text the As long as same change. the other atoms to make ble-click aniline: to change benzene to example, For 1.replaceto atom type and the hydrogen Click . Paste 70 select ------Example 2: ethane Cartesianas separa- table (tab tor) C-0.49560.57820.0037 C0.4956-0.57820.0037 H0.05521.55570.0037 H-1.15170.52520.9233 H-1.15690.5248-0.9233 H-0.0552-1.55570.0037 H1.1517-0.52520.9233 H1.1569-0.5248-0.9233 Examples Example 1: chloroethane Cartesian table as separator) (space character 0.336544 0.003670 C 0 -0.464725 -0.874491 0.003670 C 0 0.458798 1.818951 0.003670 Cl 0 0.504272 0.311844 0.927304 H 0 -1.116930 0.311648 -0.927304 H 0 -1.122113 -1.818951 0.003670 H 0 -0.146866 -0.859095 0.923326 H 0 1.116883 -0.858973 -0.923295 H 0 1.122113 preserved; otherwise is order column not important. columns be seven must there a Z-Matrix table, For eight col- column) or Number Serial (not including is included.) column Number (if the Serial umns NOT be changed.The column order must copya Cartesian intoZ-Matrix table or To Chem3D: 1.file. in the text or Excel table the Select 2. Use Ctrl+C to transfer to the clipboard. 3.a blank table in Chem3D and in Right-click

Administrator Figure 4.10 : aniline model The bond orders of the bonds change to reflect the new atom types. To change several bonds at once: 1. Open the ChemDraw panel and click in it to activate the ChemDraw control. 2. Choose either selection tool, Lasso or Marquee. 3. Click the first bond to be changed, then use Shift+Click to select the others. 4. Right-click in the selected area, and choose the bond type. Figure 4.11 : Using a context menu to change bonds

Changing Bond Order To change the bond order, you can use the bond tools, commands, or the Text tool. You can change the bond order in the following ways: • One bond at a time. • Several bonds at once. • By changing the atoms types on the bond. 5. Click in the Chem3D window to complete the To change the bond order with the bond tool: action. 1. Select a bond tool (of a different order). Bonding by Proximity 2. Drag from one atom to another to change. To change the bond order using a command: Atoms that are within a certain distance (the bond proximate distance) from one another can be auto- 1. Right-click a bond. matically bonded. 2. Point to Set Bond Order, and choose a bond Chem3D determines whether two atoms are proxi- order. mate based on their Cartesian coordinates and the To change the bond order by changing the atom standard bond length measurement. type of the atoms on either end of the bond: Pairs of atoms whose distance from each other is 1. Click the Text tool. less than the standard bond length, plus a certain 2. Shift+click all the atoms that are attached to percentage, are considered proximate. The lower bonds whose order you want to change. the percentage value, the closer the atoms have to 3. Type the atom type to which you want to change be to the standard bond length to be considered the selected atoms. proximate. Standard bond lengths are stored in the Bond Stretching Parameters table. 4. Press the Enter key. To set the percentage value:

Chem & Bio 3D 71 User Guide . Chapter 4 : O molecule. 2 View>View Focus>Set Focus to Selection Focus>Set View>View will resize and reposition the view so that all of the atoms in the view focus are visible. the view focus. centered around be the rotationresize will or the view focus. another H • Bond lengths • Bond angles • Dihedral angles • Chem3D When building with the bond tools, • added, they become new atoms are As part of • When rotating,resizing ormanually, the view 5. locationdifferent in to add a Double-click Setting Measurements go measurements to the following set any of To Structure>Measurements Figure 4.12 : H2O model fragments model : H2O 4.12 Figure View Focus As large, of the sec- keeping become models track becomes more dif- working are you ontion which you of atoms for View focus defines this set ficult. the entire By default, them in view. keeps and is in focus. model and atoms the view focus to include specific set To on: are working bonds you 1. Select the fragmentbonds. or or set of atoms 2. Go to Once you have set the view focus, the following the following set the view focus, have Once you happen: . . tab. key. The fragment appears. key.

key. The appears. fragment key. Model Building Model . Enter Enter Structure>Bond Proximate Structure>Bond File>Model Settings H2O 72 appears. substructure. adjust the percentageadjust the to the standard added the proxim- Chem3D assesses when bond length pairs. ity of atom proximity. water molecule to appear. A text box appears. A text box molecule to water appear. If they are proximate, a bond is created. If they are proximate, 4. the Press Adding Fragments fragments. A model can comprise several begin building in a cor- using are bond tools, If you thener of window. tool: are using the Text If you 1. text A box in an empty area of the window. Click 2. or type, of an element, atom name the in Type 3. the Press 1. Go to 3. to Addition% slider Proximate Bond Use the the If 0 to 100%. from value can adjust the You considered proxi- atoms are then two is zero, value is no them between mate only if the distance greaterlengthbondstandard than the bond of a is 50, if the value example, connecting them. For if the atoms are considered proximate then two greater them is no between distance than 50% connect-standardthemore thanof length a bond ing them. atoms: proximate bonds between create To 1. for bond tested want Select the atoms that you 2. Go to For example, to add water molecules to a window: to add water example, For 1.tool. the Text Click 2. a want location you in the approximate Click 3. Type The appears. ModelChem 3D Settingsdialog box 2. Select the

Administrator • Close contacts The Measurement table appears, displaying the angle value. Click the angle value in the Actual column and edit it. NOTE: When you choose Structure>Measurements, the 3. Edit the highlighted text. display of the Set Measurement option will vary, depending on what you have selected. 4. Press the Enter key. Setting Dihedral Angles When you use the Clean Up command (go to Struc- To set a dihedral angle: ture>Clean Up), the bond length and bond angle values are overridden.Chem & BioDraw tries to 1. Select four contiguous atoms. adjust the structure so that its measurements 2. Go to Structure>Measurements>Display Dihedral match those in the Optimal column of the Measure- Measurement ment table as closely as possible. These optimal The Measurement table appears, displaying the values are the standard measurements in the Bond angle value. Click the angle value in the Actual col- Stretching and Angle Bending parameter tables. umn and edit it. For all other measurements, performing a Clean 3. Press the Enter key. Up or MM2 computation alters these values. To use values you set in these computations, you must apply a constraint. NOTE: Angles in the Measurement table may be negative but equivalent values. Setting Bond Lengths To set the length of a bond between two bonded atoms: Setting close contact Distances 1. Select two adjacent atoms. To set the distance between two non-bonded 2. Go to Structure>Measurements>Display Bond atoms (an atom pair): Length Measurement. 1. Select two unbonded atoms. The Measurement table appears, displaying dis- 2. Go to Structure>Measurements>Display Distance tance between the two atoms. Click the distance Measurement. value in the Actual column and edit it. The Measurement table appears, displaying the dis- 3. Click the distance value in the Actual column and tance. The Actual value is highlighted. edit it. 3. Edit the highlighted text. 4. Press the Enter key. 4. Press the Enter key. Setting Bond Angles To set a bond angle: NOTE: You can also move an atom with the Move Objects tool. The Measurement table will automatically update. 1. Select three contiguous atoms for a bond angle. 2. Go to Structure>Measurements>Display Bond Angle Measurement.

Chem & Bio 3D 73 User Guide Chapter 4 . If the Automatically . If the Automatically andard measurement when when andard measurement field of the Measurement field of the Measurement or perform a Docking, Overlay, performOverlay, or a Docking, key. Optimal followed by the numberof the for- - Enter or Clean Up + mal charge. mal charge. 4. the Press or MM2 computation. con- the for value enter a new set constraints, To straint in the Setting Charges a formalassigned Atoms are the on charge based atom type parameter for that atom its and bonding. the atom. to pointing the charge by can display You set the formal of an atom: charge To 1.tool. the Text Click 2. Select the atom or atoms to change. 3. Type If you set the bond angle C(1)-C(2)-C(3) to 108 C(1)-C(2)-C(3) bond angle set the If you C(1) atom. moving end the C(3) becomes degrees, H(11) and H(12) move and C(2) remain stationary. partnot are they because are of the ring but bonded toatom the moving Model Building selected, is box check Rectify a rectification is because it move may tabH(10) to C(3). is positionedrelative atom and Setting Constraints can override the measurements standard that You setting con- Chem3D uses to position by atoms for optimal value an to set constraints Use straints. a particular dihedral bond length, bond angle, then is which or non-bonded distance, angle, appliedthe st instead of use you table. of dihedralIn the case angles and non-bonded dis- constraints keep that measurement con- tances, stant (or nearly so) of while the remainder the The the computation. con- by is changed model computa- from a the atoms remove doesn’t straint tion.

File>Model Settings>Model Building consider the structureFigure 4.13: in

tab (go to between two atoms, all atoms bondedthe to all atoms atoms, two between From selected non-moving atom do not move. any atoms which among the remaining atoms, atom move. are bondedmoving theto measurement moves while other atoms moves measurement same in the measurement remain describing the position. tab) is selected, rectification atoms that are atoms tab) is selected, rectification may to an atom that moves positioned relative also be repositioned. 74 • in the Model Building box check If the Rectify •settingorare length a bond the distance If you • the describes that end atom selected one Only Figure 4.13 : Cyclopentylmethanol 4.13 : Cyclopentylmethanol model Figure When you change the value of a measurement, the the measurement, a of change the value Whenyou Chem3D moves. selected last atom determines other which inatoms the fragmentsame also move repositioningby the atoms that to the are attached the atoms that are excluding atom and moving selected atoms. other to the attached are within a a measurement atomsin the If all of atomsis generated ring,fol- the set of moving as lows: Atom Movement Atom For example,

Administrator To set the formal charge of an atom in a molecular Serial Numbers fragment as you build you can add the charge after the element in the text as you build. Atoms are assigned serial numbers when they are created. To add the charge: 1. Type PhO- into a text box with no atoms Viewing serial numbers selected. You can view the serial numbers in the following 2. Press the Enter key. The phenoxide ion molecule ways: appears. • For individual atoms, use the Select tool to To remove the formal charge from an atom: point to the atom. The serial number appears in 1. Click the Text tool. the pop-up information. 2. Select the atom or atoms whose formal charge •Go to View> Model Display>Show Serial Numbers. you want to remove. •Go to File>Model Settings>Model Display tab and 3. Type +0. check the Show Serial Numbers checkbox. Click 4. Press the Enter key. Apply when finished. Displaying charges • Click the Serial Number toggle on the Chem and Bio3D 11.0 recognizes formal and delo- Model Display Toolbar. calized charges on atoms. As also shown in Chem- Reassigning serial numbers Draw drawings, Chem & Bio 3D 11.0 displays the formal charge that has been assigned to atoms and Serial numbers are initially assigned based on the calculates the delocalized charge. If an atom pos- order in which you add atoms to your model. sess a delocalized charge that is different from the To reassign the serial number of an atom: formal charge, both charges are shown; otherwise, only the formal charge is displayed. 1. In the Model Explorer, select the atoms you want to re-number. Figure 4.14 Formal and delocalized charges on 2. Right-click the selected atoms and go to Atom formic acid Serial Numbers>Hide Atom Serial Numbers.

NOTE: The Model Explorer cannot update its numbering to match the changes you are making on the model when Serial Numbers are displayed. If you forget this step, you will see different numbers on the tree control and the model. If this happens, simply hide the serial numbers momentarily and redisplay them.

3. Click the Text tool. 4. Click the atom you want to reserialize. A text box appears. 5. Type the serial number.

Chem & Bio 3D 75 User Guide Chapter 4 to to Reflect Reflect to negate all of the commands certain Reflect Through Y-Z Reflect Through . ohexylmethylamine model ohexylmethylamine Invert through Invert through Origin Reflect to negateof the Z coordi- all dihedral angles to invert. to invert. dihedral angles Structure>Invert

Reflect Through X-Z Plane X-Z Through Reflect all of the X coordinates are negated. You can all of the X coordinates are negated. You

, negate all of the Cartesian coordinates of the model. 2. the From Y coordinates. Likewise, you can choose can choose you Likewise, coordinates. Y Through X-Y Plane To invert several dihedral angles (such as all of the dihedral angles (such several invert To ring) simultaneously: a angles in dihedral 1. Select the Reflection to perform command Reflect the Use reflections model through any of the specified on your Z. or planes–X, Y, the choose When you can choose You nates. Figure 4.15 : Cyclohexylmethylamine model : Cyclohexylmethylamine 4.15 Figure The structure in Figure 4.16 is created. cycl : Inverted 4.16 Figure Plane All of the dihedral angles up the are ring that make negated. positioned Atoms ringthe axialto are repositioned equatorial. Atoms positionedequato- rial to the ring are repositioned axial. Cartesian of the atoms are coordinates of each negated. choose Whenyou choose choose for cyclohexylm- Invert . key. key. if you choose choose if you , Enter Enter Structure>Invert 76 The Invert command only repositionsThe Invert side chains extending from an atom. For example You can alter the stereochemistry of your model by by stereochemistry model the can alter of your You or reflection. inversion Inversion sym- command performs The Invert an inversion metry atom. operation about a selected chiral perform an inversion: To 1. Select the atom. 2. Go to Changing Stereochemistry 6. the Press Normally, the atoms are selected reserialized in the Normally, the However, of their currentorder serial numbers. the in four atoms selected are reserialized first them. selected order you If the serial numbers of any unselected atoms con- atoms unselected of any serial numbers If the those unse- then flict serial numbers, new the with also. are renumbered lected atoms reserialize another next sequen- atom with the To want you the next atom double-click tial number, to reserialize. atoms at once: several reserialize To 1.tool. Text the Click 2. atoms. Shift and select several Hold down 3.starting the serial number. Type 4. the Press ethylamine (Figure 4.15) around the C(1) carbon: ethylamine

Administrator If the model contains any chiral centers, each of Rectifying Atoms these commands change the model into its enantiomer. If this is done, all of the Pro-R positioned To rectify the selected atoms in your model, go to atoms become Pro-S and all of the Pro-S posi- Structure>Rectify. tioned atoms become Pro-R. All dihedral angles Hydrogen atoms are added and deleted so that used to position atoms are negated. each selected atom is bonded to the correct number of atoms as specified by the geometry for its atom type. This command also assigns atom types NOTE: Pro-R and Pro-S within Chem3D are not equiv- before rectification. alent to the specifications R and S used in standard chemistry The atom types of the selected atoms are changed terminology. so that they are consistent with the bound-to orders and bound-to types of adjacent atoms. For example, for the structure in Figure 4.17, when Cleaning Up a Model any atom is selected, go to Structure>Reflect Model>Through X-Z Plane. Normally, Chem & Bio 3D 11.0 creates approxi- Figure 4.17 : Reflecting through a plane mately correct structures. However, it is possible to create unrealistic structures, especially when you build strained ring systems. To correct unrealistic bond lengths and bond angles use the Clean Up command. To clean up the selected atoms in a model, go to Structure>Clean Up. The selected atoms are repositioned to reduce Chem3D produces the enantiomer in Figure 4.18. errors in bond lengths and bond angles. Planar Figure 4.18 : Enantiomer produced by reflection atoms are flattened and dihedral angles around double bonds are rotated to 0 or 180 degrees. Printing and Saving When you are ready, you can print your models to either an Adobe® PostScript® or non-PostScript® printer or save it in any of a variety of file formats. Printing When you print your model, you can specify a vari- Refining a Model ety of options such as the scale and resolution of the image. After building a 3D structure, you may need to clean it up. For example, if you built the model Setting Print Options without automatic rectification, atom type assign- To open the Print Setup dialog box, go to File>Print ment, or standard measurements, you can apply Setup. these as a refinement. To set up print options:

Chem & Bio 3D 77 User Guide . Chapter 4 Edit>Paste . The dialog Preferences and choose either Bitmap or and choose . . File>Preferences File>Save As Note: Bitmap will retainthe background, EMF Edit>Copy As Save a name for the file and select a file type. select a file and a name for the file Enhanced Meta File. Enter box opens. box to use as a default. want file type you filesbe saved. to 2. list the dropdown the in specify the File In tab, 3. want you file location where a default Specify are only choose Keep in mind that the options you can still select a different format You defaults. your a file. save you or location whenever 2. Copying and Embedding into application, another a model copy When you the original or ChemDraw, as Microsoft Word such can modify the copy as You is unaffected. model is 3D file and the originalChem want as you much file, the embed when you unchanged. However, file within the application. original the place you within open it from can This means that you modify the file in If you etc). (or Word, ChemDraw also modified in the ChemDraw is it Chem 3D, documentthat contains it. Copying Models a 3D structure:model as copy a To 1.select the model. In Chem 3D, 2. go to NOTE: the backgroundformat transparent.will make 3. select etc.), (or In Word, ChemDraw Saving your file 1. Go to 3. Click To Set your own defaults: own Set your To 1. Go to . File>Print of the printed page. ity. Deselect for faster printing. for faster Deselect ity. willreplace the backgroundcolor that appears on screen. the size of the page 78 to print and the number of copies. Click OK Click copies. of to print and the number when finished. the printer. use. to want you paper Printing. to use 2-Sided want whether you select • footer appears at the bottom Include a Footer- • High resolution Printing- select for higher qual- • Scale to____ mm/Angstrom • with print WhiteBackground- White Always • The Scale to Full Page- model will be resized to 6. OK. Click Chem 3D uses a default and file type location can over- you However, a file. save you whenever ride them such that Chem 3D uses defaultsa file. ofsaves time it each choosing yourown 2. want the page select you box, print dialog the In Setting Defaults Saving Models as a file so a model to save want will you Typically, import to it later or into itcome back can that you Chem another as Microsoft Word. application such for- Each of formats. in a variety save you lets 3D disad- and advantages use, specific own its mat has information on file formats, see For vantages. Appendix E. To Print 1. Go to 1.of name select the list, Printer dropdown In the 2. list, select the size o f the Form In the dropdown 3. an orientation. Select 4. printingthan more model one a time, at For 5. options: the following from Select

Administrator Chapter 5: Modifying Models

A variety of tools are available to help you modify 1. Click the Select tool . models you create. You can show or hide atoms and select groups to make them easier to modify. 2. Click the atom or bond.

Selecting NOTE: Selecting two adjacent atoms will also select the Typically, you will need to select atoms and bonds bond between them. before you can modify them. Selected atoms and bonds are highlighted in the model display. You To quickly select all atoms and bonds in a model, can change the default selection color in the Model go to the Edit>Select All or type CTRL-A. Settings dialog box. Figure 5.1: The Model Settings dialog box Deselecting Atoms and Bonds Colors & Fonts tab When you deselect an atom, you deselect all adjacent bonds. When you deselect a bond, you deselect the atoms on either end if they are not also connected to another selected bond. To deselect a selected atom or bond, do one of the following: Set selection color • Shift+click the atoms or bonds in the display window. • Ctrl+click the atom in the Model Explorer. If Automatically Rectify is on when you deselect an atom, adjacent rectification atoms and lone pairs are also deselected.

NOTE: A rectification atom is an atom bonded to only one Selecting Single Atoms and Bonds other atom and whose atom type is the rectification type for that atom. You can select atoms and bonds in the model window or by using the Model Explorer. If the Model Explorer is not active, go to View>Model Explorer to To deselect all atoms and bonds, click in an empty open it. area of the Model window. To select an atom in the Model Explorer, simply With the Model Explorer, you can use different click it. To select more than one atom, hold down selection highlight colors for different fragments either the SHIFT or CTRL key at the same time. or groups. To select an atom or bond in the display window:

Chem & Bio 3D 79 User Guide sec- from . Color by New Group Chapter 5 . tab. model appears in the model plorer or Model window, plorer window, Model or radio button in the in radio button Colors & Fonts & Fonts Colors Group File>Model Settings File>Model View>Parameter Tables>Substructures View>Parameter Color by Group is displayed or Ribbon only when tion. Each atom in your color specified for its group. change, double-click its corresponding double-click change, cell in the Color column.The appears. Color dialog box the contextmenu. select the atoms and bonds you want in the in want atoms and bondsselect the you atom first tool, select the Using the select group. atoms select the other to then use SHIFT-click and bonds. and choose selected atoms you 2.to the substructure want whose color you For 3. OK. click color and Select a 4. the Substructures Close and Save table. in the Substructures are assigned Once colors group: by can use them to apply color you table, 1. Go to If the groups model are substructures in your defined in the Substructures table (substruc- standard can assign to them. colors you tures.xml), assign (or change) a color: To 1. Go to 3. Select the NOTE: Cartoon display mode is selected. Selecting a Group or Fragment group to select a or frag- ways several Thereare Model Explorer, ment. Thethe is to use simplest select the fragment. and 2. Select the To define a group: To 1.Ex Model the In either 2.of the one right-click Explorer, In the Model Select 80 Defining Groups group. a portiona model can define as your of You to easily select and to highlight a way This provides site of a protein) part as the active of a model (such for visual effect. Any atoms that fall at least partiallyAny atoms thatfall at least the within release selection rectangle are selected when you both A bond is selected only if button. the mouse also selected. bond are the atoms connected by selected atoms selected, keep previously hold To another make while you the SHIFT key down of and all the Shift key hold down you If selection. already are the atoms within the Selection tool selected, then these atoms are deselected. Using the selection tool Using the selection and bonds using the Selec- atoms select several To tion tool, drag diagonally you the atoms across to select. want 5.2 Figure You can define groups of atoms (and fragments or You large to select models) and use the Model Explorer select groupsalso can of You the entire group. atoms withoutthem defining as a group with the selection rectangle. For more information more see For Explorer, Model the on Explorer”“Model page on information 99 for on of the Modelfunctions other Explorer. Atom Groups To change the highlight Model color in the To and choose any level at right-click Explorer, Color.

Administrator You may also select a single atom or bond. Go to 2. Right-click the selected object. From the context Edit>Select Fragment. menu point to Select and click the appropriate option: NOTE: If you want to select more than one fragment, you must use the Model Explorer. Option Result

Select Atoms Selects all atoms lying within After you have selected a single atom or bond, each within Distance of the specified distance from successive double-click will select the next higher Selection any part of the current selec- level of hierarchy. tion. Selecting by Distance Select Groups Selects all groups that contain You can select atoms or groups based on the dis- within Distance of one or more atoms lying tance or radius from a selected atom or group of Selection within the specified distance objects. This feature is useful, among other things, from any part of the current for highlighting the binding site of a protein. selection.

To select atoms or groups by distance: Select Atoms Selects all atoms lying within 1. Use the Model Explorer to select an atom or within Radius of the specified distance of the fragment. Selection Centroid centroid of the current selection.

Select Groups Selects all groups that contain within Radius of one or more atoms lying Selection Centroid within the specified distance of the centroid of the current selection.

NOTE: Atoms or groups already selected are not included. Also, the current selection will be deselected unless multiple selection is used. Hold the shift key down to specify multiple selection.

Showing and Hiding Atoms Sometimes, you may want to view your models with some atoms temporarily hidden. Use the Model Explorer to hide atoms or groups.

Chem & Bio 3D 81 User Guide . and Show model or Show All or Chapter 5 and select the Show intermolecular Show Intermolecular Show tab. Select tab. View>Model Display>Hydrogen Bonds Display>Hydrogen View>Model Settings File>Model in the list. Hydrogen Bonds drop-down All choose either choose Display • Oxygen All atoms • Nitrogen atoms in delocalized systems to •Go •Go to to •Go • *-N-H • *-O-H Figure 5.3: Hydrogen bonds in MM2 optimized water bonds Hydrogen 5.3: Figure There are separate atoms controls for hydrogen only to display can choose you and loneand pairs, (those bonded or nitro- to oxygen polar hydrogens con- you bonds, hydrogen gen). displaying with As Hydrogen Bond Acceptors: Bond Hydrogen bond,do one of the follow- hydrogen display To ing: Hydrogenrepresentedare bonds lines as dashed and the acceptor the donor hydrogen between less than ideal geometrywith Bonds atom. are dis- with a blue tint. Theplayed intensity of the color less ideal. increases as the bond becomes play only the polar hydrogen atoms in a model. atoms the polar only hydrogen play following the 11.0 recognizes & Bio 3D Chem donorbond and acceptor hydrogen groups: Hydrogen Bond Donors: and click and click Select ... and choose and select either: ... (Atom Group, Group, ... (Atom Show Hide . Show . and click and click . View>Model Display View>Model Visibility and choose and choose 82 Select All Children Select Setting Inherit atoms or groups, or Shift+click to select the or Shift+click atoms or groups, entire model. •hydrogen atoms>Show All Show •Lone Pairs>Show All Show etc). Hidden atoms or groupsetc). Hidden in are displayed in the tree control. parentheses to are set hierarchy the in all levels By default, can but you inherit the settingsabove, of the level a grouphide to reset the default individ- but show ual atoms in it. Hydrogen Bonds Hydrogen hydro- Bio 3D 11.0 can detect and display Chem & dis- canselectively also genmodel. You bonds in a Showing All Atoms be large with a model, it may working are If you hid- have everything of you track difficult to keep atomsor groups all show that are hidden: den. To 1. the hidden in the tree above control Select a level 2. point to context menu the From A check mark appears beside the command, indi- appears beside mark A check cating that selected. it has been selected, hydrogen are not Whenoptions these pairs are automatically hidden. atoms and lone Hydrogens and Lone Pairs Hydrogens and Lone lone pairs in the atoms and all hydrogen show To model, goto Showing atoms group, a hidden to an atom belonging show To tree control, point to on the atom in the right-click Visibility Hiding atoms and groups atoms Hiding at any level, hide right-click groups, atoms or To point to 3. again, Right-click point to

Administrator trol the setting either from the View menu or the 1. Click both the Model Axis and View Axis tools Model Settings dialog box. to visualize the axes. Figure 5.4: Setting hydrogen and lone-pair display NOTE: The axes will only appear if there is a model in the window.

2. Drag with the single bond tool to create a model of ethane. Display/Hide 3. Point to an atom using the Move Objects Tool. Hydrogen atoms 4. Drag the atom to a new location. Display/Hide Figure 5.5: Moving an atom Lone pairs 1

By default, Show Polar is selected when a macromo- lecular PDB or mmCIF file is loaded. These display modes are global options, but their effect can be overridden by explicitly changing the display mode of a particular atom or group in the 2 Model Explorer. Moving Atoms or Models Use the Move Objects tool to move atoms and other objects to different locations. If the atom, group of atoms, bond, or group of bonds that you want to move are already selected, then all of the selected atoms move. Using the Move Objects tool changes the view relative to the model coordinates. Dragging moves atoms parallel to the X-Y plane, The following examples use the visualization axes changing only their X- and Y-coordinates. to demonstrate the difference between different If Automatically Rectify is on, then the unselected types of moving. To move an atom to a different rectification atoms that are adjacent to selected location on the X-Y plane: atoms move with the selected atoms. To move a model: 1. With the Move Objects tool, click and drag across the model select it. 2. Drag the model to the new location.

Chem & Bio 3D 83 User Guide a r . Chapter 5 X-Axis Rotation B X-Axis Rotation Z-Axis Rotation Ba Rotation Z-Axis Rotation bar Internal Rotation Bar Y-Axis Rotation Bar Rotation Y-Axis 2. bar. pointer along the Rotation the Drag X- Y- or Z-Axis Rotations X- Y- or Z-axis: rotate a model about the X-, Y-, To 1. to the appropriate Point Rotating Models Rotating model rotate the freely to you allows Chem3D tool, select the Trackball When you around axes. on the are displayed rotation bars pop-up four these can use You periphery of the window. model modeldifferent from rotation your bars to view can You different axes. rotating around by angles use can where you dialog box the Rotate also open degrees of dial or type the number to the rotate rotate. select the Trackball bars, the Rotation display To tool edgewin- an of the model toolbar. from the Building over mouse When you edgesthe of the bars appear on the Rotation dow, Model window. model Rotating a 5.8: Figure 84 2 1 Figure 5.7: Translating a model 5.7: Translating Figure Note that the View axis has moved relative to the relative Note that the View axis has moved model coordinates. Tool The Translate tool Translate Use the tool, you use the Translate When you window. view model in the a move to model coordinates the view and the focus move position along with the model. the Thus, model’s to the origin. relative change does not Figure 5.6: Moving a model model Moving a 5.6: Figure

Administrator If Show Mouse Rotation Zones is selected on the GUI 2. Enter exact numbers into the degree text box. tab of the Preferences dialog box, the rotation bars The Internal Rotation icons are available only will pop up. This is the default setting. when atoms or bonds have been selected in the model. NOTE: The rotation bars are active when the Trackball To perform internal rotations in a model, you must tool is selected, even if they are hidden. select at least two atoms or one bond. You may then either rotate the model around the bond axis, or rotate either end. The number of degrees of rotation appears in the Figure 5.9: The Rotation dial Status bar. Rotating Fragments If more than one model (fragment) is in the model window, you can rotate a single fragment or rotate all fragments in the model window. To rotate only one fragment: degree display 1. Select an atom in the fragment you want to box rotate. 2. Hold the Shift key while dragging a rotation bar. To rotate all fragments, drag a rotation bar. Axis rotation Trackball Tool Use the Trackball tool to freely rotate a model. rotate around bond axis dihedral rotation Starting anywhere in the model window, drag the pointer in any direction The Status bar displays the X and Y axis rotation. Internal Rotations NOTE: Using the Internal Rotation Bar (the one to the left of the workspace) rotates the model around the selected bond Internal rotations alter a dihedral angle and create axis. Note that this is a change from earlier versions of another conformation of your model. You can Chem3D, where the Internal Rotation Bar rotated the dihe- rotate an internal angle using the dihedral rotators dral. on the Rotation Dial.

Using the Rotation Dial Internal rotation is typically specified by a bond. The Rotation Dial offers a quick method for rotat- The fragment at one end of the bond is stationary ing a model or dihedral a chosen number of while the fragment attached to the other end degrees with reasonable accuracy. To open the rotates. The order in which you select the atoms rotation dial. determines which fragment rotates. 1. Click the arrow next to the Trackball tool. For example, consider ethoxybenzene (phenetole).

Chem & Bio 3D 85 User Guide ,

C1 Axis of Rotation Chapter 5 Dummy atom Rotate About Bond About Rotate Rotate About Bond About Rotate . O To deselect the atoms, hold down the S key and click and click the S key hold down atoms, the deselect To then Rotation bar on the left side of the Model win- side bar on the left of the Rotation dow. Rotation bar on the left side of the Model win- bar on the left side of the Rotation dow. • order of the first selection: select Reverse Figure 5.12: Rotating Around a Specific a Around Rotating 5.12: Figure Axis around an axis: the modelrotate To 1. atoms. any two Select 2. the pointer Drag along the Rotating a Dihedral Angle select a specific dihedral angle to rotate. can You rotate a dihedral: To TIP: the model window. in anywhere a Bond Rotating Around rotate the modelaround a specific bond: To 1.bond. Select a 2. Drag the pointer along the a SpecificRotating Around Axis model around can rotate anyour You axis you model. atoms in your two any selecting by specify atoms (see can add “Undefined dummy You onBonds and Atoms” page as fragments 63) to anspecify to rotate. axis around which

C1 atom. O faded fragment is rotating keys, and select the and keys, S selection nd and key, and select the and key, S Shift selection 2 st 1 (Anchor) 86 atom. drag the Rotation Dial onto the workspace. Dial drag the Rotation • the right-hand dihedral rotator. Click 4. the left-hand dihedral rotator. Click 5. Drag the dial to rotate the phenyl group. 3. the Hold down To perform a rotation about the C-O bond where To of the following: do one groupthe ethyl moves, Figure 5.11: Selecting atoms for rotation around a bond around Selecting atoms for rotation 5.11: Figure To rotate about the C-O bond where the phenyl about the C-O bond where the phenyl rotate To group moves: 1.tool, and the arrow next to the Trackball Click 2. the Hold down Figure 5.10: Rotating around a bond 5.10: around Rotating Figure

Administrator 1. Select four atoms that define the dihedral. The model rotates so that the two atoms you select 2. Select one of the dihedral rotators on the Rota- are parallel to the appropriate axis. tion Dial. 3. Drag the dial or enter a number in the text box. NOTE: This changes the view, not the coordinates of the molecule. To change the model coordinates, Go to Struc- TIP: The keyboard shortcuts for dihedral rotation are ture>Model Position. Shift+B and Shift+N. For example, to see an end-on view of ethanol: Figure 5.13: Rotating a dihedral angle 1. Click the Select tool. 2. Shift+click C(1) and C(2). Figure 5.14: Selecting atom for alignment

You can change the orientation of your model along a specific axis. Although your model moves, the origin of the model (0, 0, 0) does not change, 3. Go to View>View Position>Align View Z Axis With and is always located in the center of the model Selection. window. To change the origin, see “Centering a Figure 5.15: Ethane aligned on the Z-axis Selection” on page 88. Aligning to an Axis To position your model parallel to either the X-, Y-, or Z-axis: 1. Select two atoms only. 2. Go to View>View Position>Align View (X, Y, or Z) Axis With Selection. Aligning to a Plane You can align a model to a plane when you select three or more atoms. When you select three atoms, those atoms define a unique plane. If you select more than three atoms, a plane is computed that

Chem & Bio 3D 87 User Guide (or Chapter 5 B C . on Origin. ) View>View Position>Align View X-Y Plane View Position>Align View>View Postion>Center Model Structure>Model With Selection With Selection selected atoms in the ring are adjacent. selected atoms in the A • Windows Resizing • Scaling a Model The model moves to the position shown in Figure in to the position shown The model moves 5.16 C. Resizing Models to ways following the Chem & Bio 3D provides model: resize your Centering a Selection When resizing a model, or before doing computa- model. the useful to center it is often tions, (or atoms) atom an to select you Chem3D allows to determine or perform the center, the calculation on the entire model. a particularmodel based on center your selec- To tion: 1. (optional) more atoms. Select one or 2. Go to Figure 5.16: Aligning to the XY plane XY to the Aligning 5.16: Figure 3. that no two carbon such atom Select the third 4. Go to choose an choose an choose (choose a (choose . . . to move a cyclohexane chair so that so chair a cyclohexane to move

. View>View Position>Align View ( View Position>Align View>View View>View Position>Align View View Position>Align View>View View>View Position>Align View X View Position>Align View>View With Axis View >View Position> Align View ( View Align Position> >View View With Selection With With Selection With ) With Selection ) With 88 Selection axis) ring, as shown in Figure 5.16 A. in shown ring, as axis plane) three alternatingPlane: X-Y atoms are on the 1. non-adjacent carbon atoms in the two Select 2. Go to For example, 3. the third atom. Shift+click 4. Go to The model moves to the position shown in Figure Figure in shown to the position Themoves model 5.16 B. minimizes the average distance between the between distance average the minimizes plane. the and atoms selected model parallel to a position in your a plane To Cartesianplane of the system: Coordinate 1. or more atoms. three Select 2.to Go The model rotates so that the computed entire The Y-Z, or X-Z plane. plane is parallel to the X-Y, of the remains in the center center of the model window. the of two and three atoms to a plane move To atoms onto an axis: 1. atoms. Select the two 2. Go to

Administrator This command places the centroid of the selected it and other atoms. All but three of the atoms in atoms at the coordinate origin. Chem & Bio 3D your structure (the first three atoms in the Z- 11.0 calculates the centroid of the selected atoms matrix which describes your model) are positioned by averaging their X, Y, and Z coordinates. If you in terms of three previously positioned atoms. do not select any atoms, the command operates on To view the current Z-matrix of a model, go to the entire model. View>Z-Matrix Table. The Zoom Tool The first three atoms in a Z-matrix are defined as follows: You can reduce or enlarge a model using the Zoom Origin atom. The first atom in a Z-matrix. All tool: . other atoms in the model are positioned (either This tool is useful whenever you want to view dif- directly or indirectly) in terms of this atom. ferent parts of large molecules. The coordinates of First Positioned atom. Positioned only in terms the model do not change. of the Origin atom. Its position is specified by a Scaling a Model distance from the Origin atom. Usually, the First Positioned atom is bonded to the Origin atom. You can scale a model to fit a window. If you have Second Positioned atom. Positioned in terms of created a movie of the model, you have a choice of the Origin atom and the First Positioned atom. scaling individual frames or the whole movie. There are two possible ways to position the Second To scale a model to the window size, do one of the Positioned atom, as described in Figure 5.17. following: Figure 5.17: Atoms in a Z-matrix •Go to View>View Position>Fit to Window. •Go to View>View Position> Fit All Frames to Win- dow to scale an entire movie. The Model To Window command operates only on the active frame of a movie. To scale more than one frame, you must repeat the command for each frame you want to scale. In the left example, the Second Positioned atom is NOTE: The Fit command only affect the scale of the model. a specified distance from the First Positioned Atomic radii and interatomic distances do not change. atom. In addition, the placement of the Second Positioned atom is specified by the angle between the Origin atom, the First Positioned atom, and the The Z-matrix Second Positioned atom. In the right example, the Second Positioned atom The relative position of each atom in your model is is a specified distance from the Origin atom. In determined by a set of internal coordinates known addition, the placement of the Second Positioned as a Z-matrix. The internal coordinates for any par- atom is specified by the angle between the First ticular atom consist of measurements (bond Positioned atom, the Origin atom, and the Second lengths, bond angles, and dihedral angles) between Positioned atom.

Chem & Bio 3D 89 User Guide Chapter 5 angle-defining atom, e stereochemical configuration B B, and the second and the second B, The terms Pro-RPro-S and Chem3Dused in to A angle-defining atom, that theangle-defining plane atom, A, such plane. parallel to the X-Y they define is which the distance-defining atom, C, directly above thethat bond joining B C and such is parallel to second the and the Y-axis, of C. somewhere to the left is A, Figure 5.20: Pro-S and Pro-R orientation orientation and Pro-R Pro-S 5.20: Figure Figure 5.19: Positioning with two angles two with Positioning 5.19: Figure NOTE: be chiral, or achiral. the how to visualize way The most convenient Pro-R/Pro-S terms are Chem3D used in to posi- examples: in the following D is described tion positionorientation atom D in Pro-S (Figure To and Pro-R orientation (Figure 5.20 B): 5.20 A) 1.first the C, Orient the distance-defining atom, 2. to be the first angle-defining Orient atom, B, position atoms bear no relationatoms bear no position to the Cahn-Ingold-Prelog R/S specification absolut the of of a chiral atom. Pro-R and Pro-S refer only position- to the ing of D and do not imply any stereochemistry for C. C may space about C for D to space about C for D 90 AB • A-B-C-D angle a dihedral By • angle A-C-D. a second By When D is positioned using two angles, there are angles, When using two is positioned D possiblepositions in two occupy: a Pro-Rand position a Pro-S position. Figure 5.18: Positioning with a dihedral 5.18: Positioning Figure In Figure 5.18 A, atom D is positioned in terms of thus angle is the dihe- the second a dihedral angle, This dihedral A-B-C-D. angledral described by planes defined the two between angle is the angle D-C-B and A-B-C. by the C-B bond, view down if you 5.18 B, In Figure as the angle angle appears then the dihedral formed atom rotation from D-C-A. A clockwise by of B indicates a in front is C to atom A when D dihedral angle. positive In the following set of illustrations, each atom D is atom each illustrations, set of following In the three previously to positioned positioned relative A. Three and are measurements B, atoms C, angles. two and a distance, D: position needed to Atom C is the Distance-Defining atom; D is placed Atom B is the First C. distance from a specified describe an and B C, Angle-Defining atom; D, angle. is the Second Angle-Defining A Atom atom. It is ways: ofD in one two used to position Positioning by Three Other Atoms Other by Three Positioning

Administrator In this orientation, D is somewhere in front of the Positioning by Bond Angles plane defined by A, B and C if positioned Pro-R, To position an atom relative to three previously and somewhere behind the plane defined by A, B positioned atoms using a bond distance and two and C if positioned Pro-S. bond angles: When you point to or click an atom, the information box which appears can contain information 1. With the Select tool, click the second about how the atom is positioned. angle-defining atom. 2. Shift-click the first angle-defining atom. Positioning Example 3. Shift-click the distance-defining atom. If H(14) is positioned by C(5)-C(1), C(13) Pro-R, 4. Shift-click the atom to position. then the position of H(14) is a specified distance You should now have four atoms selected, with the from C(5) as described by the H(14)-C(5) bond atom to be positioned selected last. length. Two bond angles, H(14)-C(5)-C(1), and H(14)-C(5)-C(13), are also used to position the 5. Go to Structure>Set Z-Matrix>Position by Bond atom. Angles. Because H(14) is positioned by two bond angles, For example, consider the structure in Figure 5.22. there are two possible positions in space about Figure 5.22: Decahydronaphthalene model C(5) for H(14) to occupy; the Pro-R designation determines which of the two positions is used. Figure 5.21: Positioning example

To position atom C(7) by two bond angles, select atoms in the following order: C(5), C(1), C(6), C(7), then choose Position by Bond Angles.

If an atom is positioned by a dihedral angle, the Positioning by Dihedral Angle three atoms listed in the information about an To position an atom relative to three previously atom would all be connected by dashes, such as positioned atoms using a bond distance, a bond C(6)-C(3)-C(1), and there would be no Pro-R or angle, and a dihedral angle: Pro-S designation. 1. With the Select tool, click the dihedral-angle The commands in the Set Z-Matrix submenu allow defining atom. you to change the Z-matrix for your model using 2. Shift-click the first angle-defining atom. the concepts described previously. 3. Shift-click the distance-defining atom. Because current measurements are retained when 4. Shift-click the atom to position. you choose any of the commands in the Set Z- Matrix submenu, no visible changes in the model You should now have four atoms selected, with the window occur. atom to be positioned selected last. 5. Go to Structure>Set Z-Matrix>Position by Dihedral.

Chem & Bio 3D 91 User Guide Set Ori- Set Chapter 5 , and choose choose , and . Structure>Set Z-MatrixStructure>Set gin Atom The selected atoms become the origin atoms for The the origin atoms become atoms selected the Z-matrix and all other are positioned atoms rel- Because current atoms. new origin the to ative no visible changesare retained, to measurements occur. the model 2. Go to . Position by Dihedral by Position using the illustration, previous using

, 92 three atoms to start the Z-matrix. choose atoms in the following order: following in the atoms choose C(7), C(6), C(1), angle a dihedral position C(10) to C(10) by in Then choose a ring. Setting Origin Atoms Origin Setting Z-matrix:origin atoms of the specify the To 1.or two, one, first the tool, click With the Select Forexample

Administrator Chapter 6: Viewing Models

You can view information about an active model in The information about an atom or bond always a pop-up or in measurement table. begins with the name of that object, such as C(12) for an atom or O(5)-P(3) for a bond. Other infor- Popup Information mation that appears depends on the preferences you choose. You can display information about atoms and bonds by pointing to them so that pop-up infor- To set what pop-up information appears, go to mation appears. File>Preferences and select the Popup Info. tab. The options are described below: You can display the following information about an atom: Cartesian Coordinates. Displays the three numerical values indicating the atom’s position • Cartesian coordinates along the X, Y, and Z axes. • Atom type Atom Type. Displays the atom type correspond- • Internal coordinates (Z-matrix) ing to the first column of a record in the Atom • Measurements Types table. • Bond Length Z-matrix. Lists the relative positions and angles •Bond Order of atoms in this model relative to the origin atom. • Partial Charge Examples of pop-up information are shown below NOTE: The Z-matrix definition includes whether the second angle used to position the selected atom is a dihedral angle or a second bond angle. If atoms other than the one at which you are pointing are selected, the measurement formed by all the selected atoms appears.

Measurements. Provides information relative to other selected atoms, such as the distance between two atoms, the angle formed by three atoms, or the dihedral angle formed by four atoms. Bond Length. Reports the distance between the atoms attached by a bond in angstroms. Bond Order. Reports the bond orders calculated by Minimize Energy, Steric Energy, or Molecular NOTE: Precise bond orders for delocalized pi systems are Dynamics. displayed if the MM2 Force Field has been computed. Bond orders are usually 1.000, 1.500, 2.000, or 3.000 depending on whether the bond is a single,

Chem & Bio 3D 93 User Guide . A blank table and select a mea- and select column, select the value you want want you column, select the value key. The model reflects the new mea- key. Structure>Measurements Actual View>Measurement Table View>Measurement { { Enter bond angles bond lengths appears in the Tables window. appears in the Tables surement. surement to generate. to change. the 2. Go to When atoms are deleted, any measurements that When atoms are deleted, any measurements Measurement the from refer to them are removed table. When you select a measurement in the Measure- the in a measurement select When you the correspondingment table, atoms are selected select atoms in your If you window. in the model model, any corresponding measurements are selected. Editing Measurements The measurements in the table are not available just for youyou canto view, also change them. model the table, in the changeWhen a value you updated.is automatically itself of a changemeasurement: value the To 1. In the 2. cell and press in the selected a new value Type Figure 6.2: Measurement table Measurement 6.2: Figure internaldisplay measurements: To 1. Go to triple bond. Computed Computed bond. triple Displays the partial the Displays charge

94 Chapter 6 Another way to view informationAnother way about your This Measurement Table. the model is to activate internalmeasurements between table can display ways. model in various atoms in your measurements sequentially several can display You the bond shows table The following in the table. andlengths angles for Ethene. The Measurement Table The Measurement Figure 6.1: The distance between adjacent hydrogen hydrogen adjacent between 6.1: The distance Figure atoms To display the popup, simply place your cursor your simply place the popup, display To an atom or bond over non-adjacent distance the two between display To select the bonds, two between atoms or the angle cur- and place your atoms or bonds (SHIFT-click) bondsatoms. orselected the one of sor over according to the currentlythe to according calculation. selected page on Molecular Surfaces” 53 “Displaying See for information to selecta calculation. on how Non-Bonded Distances delocalized, double, or or double, delocalized, fractional. be orders can bond Charge. Partial

Administrator Non-Bonded Distances Removing Measurements To display non-bonded atom measurements: You can remove information from the Measure- ment table without affecting the model. Go to 1. Select the atoms. Structure>Measurements>Clear. 2. Go to Structure>Measurements>Display Distance Measurement. Deviation from Plane The measurement between the selected atoms is added to the table. The Deviation from Plane command lets you compute the RMS Deviation from the least squares Figure 6.3: Adding measurements to a table plane fitted to the selected atoms in the model. Example:Penicillin To examine the deviation from plane for five atoms in a penicillin molecule: 1. Build a penicillin model. 2. Using the Select tool, click on S (4) atom. 3. SHIFT+click the other atoms in the five-membered penicillin ring. The molecule should appear as follows: non-bonded distance Figure 6.4: Viewing Deviation from a Plane

Optimal Measurements Optimal values are used instead of the corresponding standard measurements when a measurement is required in an operation such as Clean Up Struc- ture. Optimal measurements are only used when the Measurement table is visible. When the Mea- surement table is not visible, the standard measurements are taken from the parameter tables. To specify optimal values for particular measurements, edit the value in the Optimal column. Chem3D also uses the optimal values with the 4. Go to Structure>Deviation from Plane. Dock command. When you choose Dock from the When the deviation from plane calculation is com- Structure menu, Chem3D reconciles the actual dis- plete, the value appears in the Output window. tance between atoms in two fragments to their optimal distances by rigidly moving one fragment The result indicates that the atoms in the five- relative to the other. membered ring of penicillin are not totally coplanar; there is a slight pucker to the ring.

Chem & Bio 3D 95 User Guide Colors & . and select the Atom Properties , select Color by File>Model Settings File>Model Only the type of result can be renamed. You cannot cannot resultOnly of type the renamed. can be You tab. Fonts the calculation you want to color-code. to want you the calculation rangestoThe red. from blue second band has a rangemore refined of color. the select To to colorize. want calculations you 3.select Properties list, In the Atom drop-down 4. The first band color bands. Select one of the two 5. select the range of boxes, text In the min/max color-coding results color-coding it find perform may After you you a calculation, the model useful to graphicallyyour in identify range a calculation. If the table displays a results of can color- you results amongof the listed atoms, the falls within it on where atom based each code range. atoms: color-code To 1. Go to 2. Under NOTE: perform the calculation. SelectingAtoms it may Property view the Atom When you Table, corre- atoms in the table which not obvious be atom which see To model. spond to those in your model. The atom your in atom selectan is which, click Alternatively, will be highlighted in the table. atom in the table to highlightthe number the row or use CTRL-click Windows, model. For in your for Macintosh) to (OPTION-click SHIFT-click atoms. select multiple To rename rename a column in the Atom Property Table: To 1.the title. column Double-click 2.box. name in the title a new Type 3. outside the table. anywhere Click in parentheses)or delete the method (shown change used to . to anythingwant. you e table, displaying the displaying e table, View>Atom Property Table View>Atom 96 Chapter 6 renaming columns renaming performWhen you model,a calculation on your a new column is added to th The column title consists of the type of results. and the above) result (“Charge”, in the table shown method used to calculate the results (“Hückel”). column the can rename You Atom Property Table Features Atom Property Table can use the Atom Property table for more You can You calculationthan just displaying results. cal- identify to it rename the columns and also use culated atom properties. The Atom Property Table displays results for cal- results displays TheProperty Atom Table perform.you culations These on be calculated can another 3D Chem a model from file, a Maestro file, per- if you example, currentthe or on model. For formthe calculation, Atom Property an Huckel atom. To charge for each list the relative will Table goview the table, to Atom Properties Atom Huckel charges for benzoic acid benzoic for charges Huckel

Administrator entire range represented in the Atom Properties, When you select a record in the table, the corre- click the Scan Value Range button. sponding atom is selected in the model. Con- 6. To view the model with your options, select the versely, when you select atoms in the model, the Preview checkbox at the bottom of the dialog corresponding records are selected in the table. box and click Apply. Editing measurements 7. Click OK when finished. To edit measurements, type the new measurement Saving Results in the in the Z-Matrix table and type Enter. When you save you model, calculation results in Changing the origin the Atom Properties table are also saved. To change which atom is uses to position the others, go to Structure>Set Z-Matrix.>Set Origin atom. NOTE: The results in the Atom Property table are identical to those listed in the Output window. However, only those Cartesian Coordinates results listed in the Atom Property table are saved with the The fields in the Cartesian Coordinates table con- Model. tain the atom name and the X-, Y- and Z- coordinates for each atom. The order of atoms is determined by their serial numbers. All of the Displaying the Coordinates Tables atoms in a fragment are listed in consecutive records. Hydrogen, lone pair, and dummy atoms The coordinate tables display the position of each are listed last. atom in your model. The Z-Matrix table shows the position of each atom relative to the position of As in other tables, you can edit values in the table another atom. The Cartesian table displays the X-, and the model will automatically update to reflect Y-, and Z-coordinates of each atom relative to a the change. fixed position in space. To display the Cartesian Coordinates table, go to View>Cartesian Table. The Cartesian Coordinates Z-Matrix Coordinates table appears. The first atom in the Z-Matrix table is defined as the origin atom. All other atoms in the table are Comparing Models by Overlay listed with their corresponding positions relative to Use the overlay feature to lay one molecule on top the origin atom. of another. This is useful for when you want to To display the Z-Matrix table, go to View>Z-Matrix compare structural similarities between models Table. with different compositions or compare confor- Figure 6.5: The Z-Matrix table for benzene mations of the same model. Chem & Bio 3D 11.0 provides two overlay techniques. “Tutorial 6: Overlaying Models” on page 35 describes the fast overlay method. This section uses the same example—superimposing a molecule of Methamphetamine on a molecule of Epi- nephrine (Adrenalin) to demonstrate their structural similarities—to describe the Minimiza- tion Method.

Chem & Bio 3D 97 User Guide column and Optimal in the Methamphetamine in the Methamphetamine into the 0 key. C(27) . in the Epinephrine molecule. Enter Structure>Measurements>Display Distance Atom Pair consists of twoare that atoms a speci- Atom Pair C(9) molecule. molecule. Measurement press the least three atom pairs, although it can be done least three atom pairs, steps Repeat 1 to 3 to create pairs. with only two at least three atom pairs. for any atom pair zero be to ments are assumed each For that appears in the Measurement table. type atom pair, 3. Go to Your measurement table should look something table measurement Your this: like The atom labels and serial numbers appear for all appear The labels atom serial numbers and atoms. the visible first identify atom must you perform an overlay, To then fragment, each in selecting an atom pairs by table. the Measurement in pairs the atom display Figure 6.7: Adding optimal values for overlay to the optimal values for Adding 6.7: Figure table Measurement NOTE: ficed distance apart and aredifferent in fragments. 1. Select The Measurement table appears. The cell Actual The Measurement table appears. currenttwo the the contains distance between atoms listed in the Atom cell. at specify must 4. you an acceptableoverlay, For 5. frag- two The optimal distances for overlaying 2. SHIFT+click . . key. Enter key. A mol- key. Enter how Atom Symbols and press the and press the and press . View>Model Display>S View>Model Serial Numbers Display>Show View>Model View>Model Display>Show Hydrogen Display>Show Hydrogen View>Model File>New Epinephrine Methamphetamine To move only one of the models, select an atom in it an atom in select moveonlymodels, one of the To 98 Chapter 6 Atoms>Hide Go to View>Model Display>Show Lone Pairs>Hide Lone Display>Show Go to View>Model ecule of Epinephrine appears. Epinephrine of ecule appears. appears. box A text rine molecule. model window. A text box appears. A text box model window. 8. Go to 9. Go to TIP: before rotating. 6.6: Overlaying models Figure The hydrogen atoms and lone pairsThe in the molecule hydrogen are hidden. the in shown appearmolecules as should The two or move need to may illustration. You following shown. them as models to display rotate the 4.Epineph-the below window, in the model Click 5. Type 7. 1. Go to 2. in the click tool and Building Text the Select 3. Type A molecule ofappears MethamphetamineA molecule beneath the Epinephrine molecule. 6. Go to

Administrator Now perform the overlay computation: Figure 6.9: Measurement table after overlay

NOTE: To help see the two overlaid fragments, you can color a fragment. For more information see “Model Explorer” on page 99

1. Go to View>Model Display and deselect Show Your results may not exactly match those Atom Symbols and Show Serial Numbers. described. The relative position of the two frag- 2. Go to Structure> Overlay>Minimize. ments or molecules at the start of the computation The Overlay dialog box appears. can affect the final results. Figure 6.8: The Overlay dialog box Model Explorer The Model Explorer displays a hierarchical tree representation of the model. It provides an easy way for you to explore the structure of any model, even complex macromolecules, and alter display properties at any level. Use the Model Explorer to: 3. Type 0.100 for the Minimum RMS Error and 0.010 for the Minimum RMS Gradient. • Define objects. The overlay computation will stop when either the • Add objects to groups. RMS Error becomes less than the Minimum RMS • Rename objects. Error or the RMS Gradient becomes less than the • Delete objects, with or without their contents. Minimum RMS Gradient value. 4. Click Display Every Iteration. The display properties of objects you can alter 5. Click Start. include: How the fragments are moved at each iteration of • Changing the display mode. the overlay computation is displayed. • Showing or hiding. To save the iterations as a movie, click the Record • Changing the color. Each Iteration check box. At the atom level, you can display or hide: To stop the overlay computation before it reaches the preset minimum, click Stop Calculation on •Atom spheres the toolbar. •Atom dots The overlay and recording operation stops. • Element symbols The following illustration shows the distances • Serial numbers between atom pairs at the completion of the over- To display the Model Explorer, Go to View>Model lay computation. The distances in the Actual cells Explorer. are quite close to zero.

Chem & Bio 3D 99 User Guide File>Pref- . Show Bonds hild” groupshild” the within tab, select tab, GUI When solventsimporting will some- PDB models, . In the erences NOTE: savefile again. the PDB Backbone featureThelets object thatis a display Backbone the carbon-nitrogenshow structureyou backbone a protein.It appearsof in the Modela Explorer as separate Theobjectno with children. atoms and to belong other up the backbone bonds that make but are also virtual of groups, and children chains dis- to select This you object. allows the Backbone the that override properties for the backbone play properties and groupsdisplay of the chains above them in the hierarchy. Atoms object in the Model Explorer repre-atom Each be Atoms cannot model. sents one atom in your deleted an If you outside the fragment. moved fragment (or a groupatom from a within frag- a itselfchanged. ment) the model is Bonds in the default do not appearobjects by Bond go bonds, to display To Model Explorer. Solvents groupa special object is Theall containing Solvent The molecules in the model. individ- of the solvent as “c ual molecules appear not be object should A Solvent object. Solvent object. of any other child times show up in chains. Chem3D preservestimes show up in chains. this structure to Group objectsGroup can consistofgroups, atoms other does Chem3D groupa limit not to bonds. and though this is the atomscontiguous and bonds, logical definition. Inherit Set- . Thisthatmeans “parents” determine the 100 Chapter 6 •Fragments • Solvents •Chains •Backbone •Groups •Atoms •Bonds properties of “children”, until you choose to properties choose until you of “children”, some By changing property of a change a property. can better visualize the part object, you level lower to study. want you model the of The are: Model Explorer objects Chains and groups and groups chains are functionally In Chem3D, are special groupsidentical. Chains in PDB found a grouprename or vice If you as a chain, files. Thisreason the also is the icon will change. versa, the menus. is used in “Group” word that only the chains. to apply also commands Group All Fragments object representsThelevel the highest Fragment repre- Fragments a model. of (“parent”) segment start if you sent separate parts of the model, that is, trace cannot at an atom in one fragment,you through a seriesatoman that connect to of bonds between create a bond in anotheryou fragment. If Chem3D will collapse the hierar- atoms, such two structure chical fragment. Fragment to create one but and groups, objects typically consist of chains and bonds. atoms also contain individual may The Model in termsthe model defines Explorer of Every“objects”. of properties, object has a set including a property thatdefinesor whether not it of a higher “child” abelongsobject to another (is “parent” object.) level The default setting for all properties is Model Explorer Objects Explorer Model ting

Administrator Managing Objects 1. Do one of the following: • In the Model Explorer, hold down the CTRL Object Properties key and select atoms you want on the group. To view or change an object property: • In the Model window, hold the SHIFT key and 1. Select the object (fragment, group, or atom) you select the atoms you want in the group. wish to change. 2. In the Model Explorer, right click your selection and choose New Group from the context menu. TIP: To select multiple objects, use Shift+click if they are 3. If you want, rename the group by typing a new contiguous or Ctrl+click if they are not. name. Adding to Groups 2. Right-click the object and select the appropriate You can add lower level objects to an existing submenu, and choose a command. group, or combine groups to form new groups. When you change an object property, the object To add to a group: icon changes to green. When you hide an object, the icon changes to red. Objects with default prop- 1. In the Model Explorer, select the objects you erties have a blue icon. want to add, using either SHIFT+click (contiguous) or CTRL+click (non-contiguous). Figure 6.10: Icons in the Model Explorer 2. Right-click your selection and choose New Group from the context menu. 3. Rename the group, if desired.

hidden NOTE: The order of selection is important. The group or changed chain to which you are adding should be the last object selected.

Deleting Groups You can delete the group without affecting its objects or the model. You can also delete the group Groups and all the objects within it. • Select Delete Group to remove the grouping Creating Groups while leaving its contents intact. Some models, PDB proteins for example, have • Select Delete Group and Contents to delete the group information incorporated in the file. For group from the model. other models you will need to define the groups:

Chem & Bio 3D 101 User Guide playing Models” on page on Models” playing box indicates the structure box is hid- in the box indicates the structure in the box is in box indicates the structuresthe indicates selected. box is empty check gray Structure Browser Structure ment to another. (For example, you cannot you example, (For ment to another. atoms from one molecule to another.) move • objects cannot from one click-drag frag- You •cannot rearrange atoms within a group. You den; a Display Modes ofOne means bringingout a particular parta of The usual mode. the display changing is by model (see “Dis apply limitations only available will display 45). Thesubmenu modes. the effect of changing the Figure 6.11 shows HEM155 group of PDB-101M from Wireframe (the default) to Space Filling. that contain as SD files, can import such files, You dozens. or even three, structures—two, multiple can browse you Using the StructureBrowser, structuresin through the list of one and view each the Model window. Structures Viewing structureeach can view or hide in the browser You selecting or deselecting its correspondingby check- A box. view; an Nesting Objects Nesting For put can also objects in other objects. You a DNA fragment that con- have can you example, helix groups that,tains two in turn, contains acid groups. nucleic in mind when you There things to keep a few are objects: move move an object, simply click-drag it from one it from click-drag simply object, an move first objects, several move To group or another. or SHIFT- using either CTRL-click select them click.

Apply Group Color Apply . . nt to highlight differ- Reset Children to Default OK on the context menu. Themenu. on the context Inherit Group Color Inherit Group Select Color 102 Chapter 6 Color Dialog box appears. DialogColor box and select 3. and click Choose a color To revert to the default color: To 1. Select the group or groups. 2. selection. your Right-click 3. go On the context menu, to command on the context menu. on the command Not only can you group objects togetherNot only can you but you This of groups. them in and out can also move wa when you becomes useful Resetting Defaults use the changes, remove To Moving Objects To ent partsassign model or attributes. of your Coloring Groups assigning differ- by models is to view Another way Changingent colors a group to groups. color in the set- standard color the Model Explorer overrides table and the SubstructuresElements tings in the table. change a group color: To 1.a group Select groups. or 2. Choose Figure 6.11: Changing display types types in display Model the Changing 6.11: Figure Explorer

Administrator The structure browser lets you quickly scan Model Explorer drag and drop through the list of structures, viewing them individually. This becomes quite useful when you want You can copy any fragment in the Model Explorer to find a model of a specific design or overlay a to the Structure Browser. Simply click and drag the model to one that is already on screen. fragment from one window to the other. Keep in mind that if you delete the fragment in the Model To scan through the structures, deselect all struc- Explorer, it is also removed from the Structure tures and use the Up/Down arrow keys on your Browser. keyboard. Each structure you select appears in the Model window. To delete one or all structures from the Structure Browser, right-click a structure in the list and select Viewing Structure Properties either Remove Object or Remove all Objects. If you want, you can also display basic properties To sort the list by a particular column, click the for each structure in the list. column title. 1. Right-click anywhere in the structure browser Adding to your Model and choose Select Properties to Display from the Although the Model Window displays the struc- context menu. tures listed in the structure browser, these struc- 2. In the Property Selection for Display dialog box, tures are not part of your model file. To add a select one or more properties you want to appear structure, click and drag it from the Structure in the list. Browser to the Model Explorer. After the structure 3. Also in the Property Selection for Display dialog is in the Model Explorer, you can treat it the same box, arrange the properties how you want them as any other fragment. to appear in the Structure Browser. Click each property and use the Up/Down arrows to move fast overlay them. Use this feature to overlay all the objects in the Structure Browser onto the structure that is selected in the Model window. NOTE: If there are no properties associated with the listed structures and you want to remove the property columns, 1. In either the Model window or Model Explorer, right-click the list and select Remove Property Columns. select the target structure 2. Right-click anywhere in the Structure Browser and select fast overlay in the context window.

Chem & Bio 3D 103 User Guide 104 Chapter 6

Administrator Chapter 7: Exporting Models

You can export a model to other applications as a 3. In the other software application, paste the picture or in chemical notation. Two graphic for- model into an open file. For example, in Chem- mats are available: bitmap and EMF; and, three Draw, go to Edit>Paste. notation formats: ChemDraw structure, SMILES, and InChI™1. NOTE: The model is imported as a bitmap or EMF graphic and contains no structural information. NOTE: Chemical notation formats are mostly suitable for exporting smaller models. You should be aware of the limitations of the format before using it. To transfer a model as a 2D drawing: 1. Select the model. You can also export an embedded object that uses 2. Go to Edit>Copy As>ChemDraw Structure. the Chem & Bio 3D ActiveX Control to manipu- 3. In the other software application, paste the late the object. model into an open file. For example, in Chem- Draw, go to Edit>Paste. The model is pasted into Using the Clipboard ChemDraw. When exporting in a graphic format, the size of the SMILES and InChI™ file that you copy to the clipboard from Chem & To copy the model as a SMILES or InChI string, Bio 3D is determined by the size of the Chem & select the model and go to Edit>Copy As and Bio 3D model window. If you want the size of a choose either SMILES or InChI. copied molecule to be smaller or larger, resize the model window accordingly before you copy it. If Embedding Models the model windows for several models are the Embedding and copying are similar in that, in both same size, and Fit Model to Window is on, then the instances, your model appears in another applica- models should copy as the same size. tion when you are finished. However, when you Copying to other applications embed your model, the model remains a Chem & Bio 3D file. This means that you can select your You can transfer information to Chem & BioDraw, model in the application and open it for editing. MicroSoft Word, PowerPoint®, and other desktop However, when you copy the model, it is simply an applications as a 3D picture or as a 2D drawing. image file and cannot be opened in Chem & Bio To copy and paste a model as a 3D picture: 3D 11.0. 1. Select the model. The improved Chem & Bio 3D 11.0 ActiveX con- 2. Go to Edit>Copy As and choose either Bitmap or trol allows you to embed animated models in Pow- Enhanced Metafile. erPoint® presentations, Word documents, or 1. InChI™ is a registered trademark of the Interna- HTML-based documents. tional Union of Pure and Applied Chemistry. InChI™ Material in Chem & Bio 3D is © IUPAC To embed a model: 2005.

Chem & Bio 3D 105 User Guide will rock the model on will rock axis speed (angle) Shows/hides right-click right-click Shows/hides Shows/hides the Rotation the Rotation Shows/hides x 1 45 DeterminesTool- the placement of Cannot be changed. Cannot be changed. Normally left blank. You can reference reference can Normallyblank. You left Cannot be changed. Specifies the model rotation. Enter data Specifies the model Definestheheight the object window. of Defines the placement of the left edge the placement Defines of the the X axis at speed 1 through an angle of 45°. the X axis at speed 1 through an angle ShowContextMenu. in the object window. menus ShowRotationBar. toolbar. ShowToolbar. toolbar. bottom)the or hides bar (left, right, top, Angle can be X, Y, or Z or a combination, for Angle can be X, Y, be 0-5, but the default may Speed XY. example: Specifying results. best of 1 generallysetting gives rather than rock model will thatmeans the an angle example, spin. For Figure Changing 3D display & Bio 7.2: Chem properties Figure the properties are can changebelow in Listed you an embedded object. DataURL. slide pre- the but cut-paste, a file rather than using later. file to that access not have sentation may EncodeData. Fullscreen. Height. Left. object window. Modified. Rotation. format:in the following pre- ® . from the context (right-click) context (right-click) the from or Ctrl+V. or Ctrl+V. Edit>Copy As>Embedded Object Edit>Copy Modifying the embedded image in HTML is Modifying the embedded image in HTML is Properties 106 Chapter 7 Edit>Paste entire model, or drag a rectangle with the Select Select the with drag a rectangle model, or entire tool. sentation, you can modify the display properties. properties. can modify the display sentation, you Select menu. 3.the object in the target document using Paste folder. folder. PowerPoint in a model a embed When you NOTE: Figure 7.1: Chem & Bio 3D in embedded model Figure FrontPage 1. the select to combination key Ctrl+A the Use 2.to Go beyond the scope of this document. If you areyou the scope of this document. If a programmer beyond see developing pages, 3D modeling HTML Bio 3D application Chem & in the ReadMeC3DP.htm

Administrator Top. Defines the top of the object window., mea- Figure 7.3: Background with logo sured from the top of the slide. Visible. Shows/hides the object window. Width. Defines the width of the object window. Background Effects and Images Chem & Bio 3D 11.0 has nearly two dozen background effects for presenting images. You can also insert an image into the background, to display your company’s logo or for visual effect. Figure 7.3 shows the “Sea and Sky” background with an embedded logo GIF file.

Chem & Bio 3D 107 User Guide 108 Chapter 7

Administrator Chapter 8: Force Field Calculations

A force field is an industry accepted term for any MM2 and MMFF94 may be viewed as different calculation method used to predict molecular calculation techniques you use to arrive at a speci- properties. For example, you may want to use a fied result. Which technique you use depends on force field calculation to predict the torsional con- your type of model and the property you want to straint for a particular bond or perhaps the repul- calculate. For example, for a given model, you may sion forces between molecules. Force fields are find that one method provides a better potential commonly used for a wide variety of calculations energy prediction than the other. Meanwhile, the and are often verified with experimental values. other method may produce charge values that are closer to experimental values. Here we describe About Atom Types each of these methods and the calculations you can perform using them. Before Chem & Bio 3D performs force field calculation, it takes into account the type of each atom MM2 in your model. An atom’s type is more than just the element it represents. It also takes into account the The MM2 force field method is available in all ver- functional group to which it belongs and its loca- sions of Chem & Bio 3D. MM2 is most commonly tion in your model. For example, a carboxyl carbon used for calculating properties of organic molecu- has a different atom type than an alkyl carbon. lar models. The MM2 procedures described assume that you understand how the potential You may be tempted to think of atom types as energy surface relates to conformations of your building types. However, there are distinct differ- model. If you are not familiar with these concepts, ences. Building types describe only an atom’s con- see “MM2.” tribution to the structure of a model-- its bond angles and bond lengths. The atom type describes the atom’s contribution to bond energies, thermal NOTE: In Chem & Bio 3D 11.0, the MM2 atom type properties and other characteristics. The force is used for force field calculations. In earlier versions, MM2 fields use this data to calculate properties of your was used only in building models. model and predict the behavior of the molecule it represents. MMFF94 Force Fields Use MMFF94 to perform energy minimization cal- Chem & Bio 3D offers two commonly accepted culations on proteins and other biological struc- force field calculation methods, MM2 and tures. The MMFF94 force field is available in MMFF94. These methods are designed so that you Bio3D and Chem 3D Ultra. can calculate molecular properties of your models. Each of these methods enable you to calculate a Displaying MMFF94 Atom Types variety of steric energy, thermal energy, and other You can display the MMFF94 atom types for your values. Results are saved as part of the atom prop- model without performing calculations. The Atom erties.

Chem & Bio 3D 109 User Guide View the dialog box, select dialog box, Do MMFF94 Minimi- Select this option to Select this option add to the time required ying or recording each ying or recording each Calculations>MMFF94> Do MMFF94 Minimization when finished: any of the following options as desired andany of the following click zation Run the energy. Display Every Iteration. during the calculation process. the model view in mind that displa Keep significantly iteration may to minimize the structure. MeasurementsOutput Box. to Copy value of each measurement in the Output window. measurement in the Output of each value beforeCalculation. Types Atom new Setup will Whenselected, Chem & Bio 3D this option is have delete types you any custom MMFF94 atom this optionmodel. Deselect you if for your defined want to keep them. beforeCharges Calculation. Atom new Setup When & Bio 3D 11.0 Chem this option is selected, entered have will replaceyou any customcharges to retain want If you in the AtomProperty table. entered, deselect this option. have the charges you Energy Minimization using MM2 using Minimization Energy minimize the energy on based of the molecule To Field: Force MM2 1. to minimize want you Build the model for which Minimizing model energy Minimizing performcan either a minimization using of You or MM2. the force fields–MMFF94 MMFF94 using Minimization Energy perform minimization: MMFF94 an To 1. Go to 2. In the http://www.cambridgesoft.com/services/faqs.cfm?FID=3 from the Product select Chem3D site, Web At the list. dropdown to view the . 94>Calculate MMFF94 94>Calculate MMFF94 94>Set Up 94>Set Up MMFF94 . . View>Atom Property Table View>Atom Calculations>MMFF View>Atom Property Table View>Atom Calculations>MMFF 110 Chapter 8 Energy and Gradient and Energy Atom Types and Charges Types Atom results. 2. Go to Energy Minimization common applications for either of the most One method is performing energy minimization calcu- the location model, you build When you lations. not accurately represent the may atom for each model Your the actual molecule. in location atom’s depict high-energymay bonds or strain at various As a result, conformational atoms. between strain represent accurately not the mole- model may your cule. consider perform- may correct model, you your To energying an MM2 or MMFF94 minimization cal- examines 3D Chem & Bio do, Whenculation. you It types. atom model and identifies its various your then calculates atoma new position so that of each potential energy is model for your the cumulative new position, calculated each Having minimized. model your in atom each moves Chem & Bio 3D so that the total energyminimum. is at a cannot energy minimize in models containingYou phosphate For groups with double bonds. drawn information to create a model with phos- on how see the Chem3D phate groupsminimize, can you at: FAQ Drawing 2.to Go energy Calculating potential can performof calculation an MMFF94 the You to need don’t potential energy model. You your for perform an energy minimization beforehand. 1. Go to Property its and atom,atomtype, its each table lists charge. in your types list of MMFF94 atom view the To model: 1.to Go

Administrator 2. To impose constraints on model measurements, Figure 8.1: The Minimize Energy dialog box set Optimal column measurements in the Mea- surement table (go to View>Measurement table). 3. Go to Calculations>MM2> Minimize Energy. The Minimize Energy dialog box appears. 4. In the Minimization Energy dialog box, select any of the following options as desired and click Run when finished:

Minimum RMS Gradient. Specify the conver- Minimum RMS Gradient gence criteria for the gradient of the potential energy surface. Use a large values for shorter calculation time but less accurate results. Use a smaller value for more accurate results but longer calculation time. The default value of 0.100 is a reasonable compromise between accuracy and speed. Display Every Iteration. Select this option to view the model during the calculation process. NOTE: If you plan to make changes to any of the MM2 Keep in mind that displaying or recording each constants, such as cutoff values or other parameters used in iteration may significantly add to the time required the MM2 force field, first make a backup copy of the param- to minimize the structure. eter tables. This will ensure that you can get back the values Copy Measurements to Output Box. view the that are shipped with Chem3D, in case you need them. value of each measurement in the Output window. Select Move Only Selected Atoms. restrict movement of a selected part of a model during the NOTE: Chem & Bio 3D 11.0 guesses parameters if you minimization. Constraints are not imposed on any try to minimize a structure containing atom types not sup- term in the calculation and the results are not ported by MM2 (such as inorganic complexes where known affected. parameters are limited). You can view all parameters used in the analysis using the Show Used Parameters command. See “Showing Used Parameters” on page 120.

Iteration data appears in the Output window when the minimization calculations begin. The data is updated for every iteration of the computation, showing the iteration number, the steric energy value at that iteration, and the RMS gradient. (However, if you have not selected the Copy Mea- surements to Output option, only the last iteration is displayed). After the RMS gradient is reduced to less than the requested value, the minimization ends, and the

Chem & Bio 3D 111 User Guide , H(7) in that order. H(4) , and The values of the energy of the The values termsare shown approx- C(1) , C(2) shown in the figure below by Shift+clicking Shift+clicking by in the figure below shown NOTE: to calculate them. Dihedral angles of one of the dihedral angles that view the value To contribution: Waals der tocontributes the 1,4 van 1. Select the atoms up making the dihedral angle as Figure 8.2: Output for staggered ethane model ethane model staggered Output for 8.2: Figure The total steric energy for the conformation is term of 0.8180 kcal/mol. der TheWaals 1,4 van This term the steric energy. dominates 0.6756 is repulsiondue to the H-H contribution. imate and can vary slightly based on the type of processor used . . dialog box. utation is in progress Computing Computing in the Minimize Energybox. dialog in the View>Model Display>Show Serial Numbers View>Model Energy Calculations>MM2>Minimize View>Model Display>Display Mode>Ball & View>Model Run . Stop 112 Chapter 8 Stick Thecalculationof the in the Output appear results bar to view all the use the scroll necessary, If box. results. 2.of ethane in an empty window. a model Draw 3. Go to Example: Minimizing Ethane of minimization, examplesimple Ethane is a one minimum-energy it has only because (staggered) maximum-energyand one con- (eclipsed) formation. minimize energy in ethane: To 1. Go to Multiple Calculations models several can minimize you want, If you a comp If simultaneously. model, begin the minimizing a second when you until delayed secondminimization of the is model one stops. the first can run you otherusingare applications, If you in the background.minimization with Chem3D can perform any action in Chem3D thatdoes You add, or delete any part not of the model. move, For around windows during can move you example, model. or scale your changeminimization,settings, final steric energy components and total appear in window. the Output Intermediate appear in the messages status may A messageif the minimi- appears Output window. zation terminates abnormally a (usually by caused poor starting conformation). interrupt that a minimization is in progress, To click 4. Go to 5. Click

Administrator 2. Go to Structure>Measurements>Display Dihedral Figure 8.5: Minimized ethane, end-on view Measurement. The following dihedral angle measurement appears. Figure 8.3: Dihedral measurement for ethane

The displayed angle represents the lowest energy When the minimization is complete, the model conformation for the ethane model. conforms to the eclipsed structure in Figure 8.5 and the reported energy values appear in the Out- Using constraint values put window as shown in Figure 8.6. The energy for Entering a value in the Optimal column imposes a this eclipsed conformation is higher relative to the constraint on the minimization routine. You are staggered form. The majority of the energy contri- increasing the force constant for the torsional term bution is from the torsional energy and the 1,4 van in the steric energy calculation so that you can opti- der Waals interactions. mize to the transition state. 1. Select the Trackball tool. NOTE: The values of the energy terms shown here are 2. Reorient the model by dragging the X- and Y- approximate and can vary slightly based on the type of pro- axis rotation bars until you have an end-on view. cessor used to calculate them. Figure 8.4: Ethane model, end-on view Figure 8.6: Output for eclipsed ethane model

To force a minimization to converge on the transition conformation, set the barrier to rotation: 1. In the Measurement table, type 0 in the Optimal column for the selected dihedral angle and press the Enter key. 2. Go to Calculations>MM2>Minimize Energy. The Minimize Energy dialog box appears. 3. Click Run. The dihedral angle in the Actual column becomes 0, corresponding to the imposed constraint. The difference in energy between the global minimum (Total, previous calculation) and the transi-

Chem & Bio 3D 113 User Guide . Run Calcula- and click and click . nimized, or innimized, or the Chem- . Edit>Select All Edit>Select Up Structure>Clean The Clean Up command isveryUp command The Clean similar to the tions>MM2>Minimize Energy Energy tions>MM2>Minimize When the minimization is complete, reorient the When is complete, the minimization as figure below. in the so it appears model The conformation to is not the converged you conformation, chair well-known is the glo- which on Instead, the model has converged bal minimum. the conformation. twisted-boat a local minimum, This is the closest low-energy conformationto startingyour conformation. built this structureHad you substructures using energythat are already mi con- be close to the chair would panel, you Draw formation. Theminimizer not surmount does the saddle point to locate the global and the minimum, sought. is closest minimum The energy should be in the Output window values follows: as approximately NOTE: mization of the structure. perform go the minimization, to To model Minimized cyclohexane 2.to Go minimizeenergy preset,in that it is a command short mini- the ability of the Minimize Energy Minimize of the the ability to command point. a minimum reach 1.to Go com- key. icon on the icon on Enter column for the column for MM2 Clean Up Structure Optimal and press the CAUTION . An empty model window window An empty model . File>New CH2(CH2)5 114 Chapter 8 appears. 2. Building tool. Select the Text 3. appears. A text box in the model window. Click 4. Type dihedral angle. Then, click the Then,click dihedral angle. method described to follow this example. to follow described method the Before minimizing, use While there are other, perhaps easier, methods of perhaps easier, Whilethere other, are the use should model, you cyclohexane creating a Example: Cyclohexane compare the cyclo- example you In the following hexane twist-boat conformation glo- and the chair bal minimum. build a model of cyclohexane: To 1. Go to tion state (Total, this calculation) is 2.50 kcal/mole, kcal/mole, this calculation)2.50 is (Total, tion state agreement in is values. literature with which further points about minimization, illustrate To from the value delete the mand to refine the model. This generally improves model. Thisrefine the mand to generally improves Calculation toolbar. Calculation are stillat you complete, is minimization After the This is an important 0 degrees. for consideration It uses first minimizer. the MM2 with working of energy to determinederivatives the next logical saddle for However, the energy. to lower move the region is fairlypoints (transition states), flat and is a minimum that satisfied the minimizer is starting suspect your point is not a If you reached. try minimum, setting by angle off dihedral the about 2 degrees minimize again. and

Administrator Figure 8.7: Energy values for twisted boat conformation 1. Drag C1 below the plane of the ring. The cursor appears as a box with a hand. 2. Drag C4 above the plane of the ring. Figure 8.8: Changing a dihedral angle 1a 2a

1b 2b

The major contributions are from the 1,4 van der During dragging, the bond lengths and angles were Waals and torsional aspects of the model. deformed. To return them to the optimal values before minimizing, select the model by dragging a For cyclohexane, there are six equivalent local min- box around it with the Select tool, and run Clean ima (twisted-boat), two equivalent global minima Up. (chair), and many transition states (one of which is the boat conformation). Now run the minimization: Locating the Global Minimum 1. Go to Calculations>MM2>Minimize Energy and click Run. Allow the minimization to finish. Finding the global minimum is extremely challeng- 2. Reorient the model using the rotation bars to see ing for all but the most simple molecules. It the final chair conformation. requires a starting conformation which is already in the valley of the global minimum, not in a local minimum valley. The case of cyclohexane is straightfor- NOTE: The values of the energy terms shown here are ward because you already know that the global approximate and can vary slightly based on the type of pro- minimum is either of the two possible chair con- cessor used to calculate them. formations. To obtain the new starting conformation, change the dihedrals of the twisted conformation so that they represent the potential This conformation is about 5.5 kcal/mole more energy valley of the chair conformation. stable than the twisted-boat conformation. The most precise way to alter a dihedral angle is to For molecules more complicated than cyclohexane, change its Actual value in the Measurement table where you don’t already know what the global min- when dihedral angles are displayed. An easier way imum is, other methods may be necessary for to alter an angle, especially when dealing with a locating likely starting geometries for minimiza- ring, is to move the atoms by dragging, then clean- tion. One way of accessing this conformational ing up the resulting conformation. space of a molecule with large energy barriers is to perform molecular dynamics simulations. This, in To change a dihedral angle: effect, heats the molecule, thereby increasing the

Chem & Bio 3D 115 User Guide causes the molecular dynamics causes the molecular dynamics determines the interval at which tab to enter parameter values for for values parameter tab to enter determines the time between . Dynamics Run the parameters that define the molecular dynamics the parameters that define the calculations: Step Interval. The step interval steps. molecular dynamics must than ~5%of the vibrationbe less period for the highest frequency normal (10 fs for a 3336 mode, vibration). NormallyH–X stretching cm-1 step a interval of 1 or 2 fs yields reasonablestep intervals cause the integration may method to results. Larger because higher order of the moments break down, position are neglected in the Beeman algorithm. Frame Interval. frames and statistics are collected. A frame interval smooth sequence of a fairly fs gives or 20 10 of frame interval and a or more can fs 100 of frames, of conformationalsamples to obtain be used space longer a computation. over Terminate After. run of steps. to stopspecifiedthe afternumber Dynamics Settings Use the Figure Molecular The 8.9: dialog Dynamics box. Figure 5. values. Enter the appropriate 6. Click ecular Dynamics. Structure>Measurements>Set Bond Angle Bond Structure>Measurements>Set Length Bond Structure>Measurements>Set Calculations>MM2>Mol The model display useaffects type you the speed of 116 Chapter 8 ments), using MM2 or MOPAC. ments), using MM2 do select the appropriate atoms and simulation, the following: one of include in the computation. •Go to to •Go •Go to to •Go 4. Go to appears with Thedialog box Molecular Dynamics values. the default faces. 2. Minimize the energy of the (or model frag- 3. a particulartrack during the measurement To NOTE: Molecular Dynamics Molecular to mechanics Newtonian uses Dynamics Molecular subtracting or adding motion atoms, of simulate increases temperature kinetic energy as the model’s or decreases. access the con- to you allows Molecular Dynamics storing a model by to formational space available run of the molecular dynamics iterations later and frame. examining each perform simulation: a molecular dynamics To 1. to want that you fragments) (or Build the model kinetic energykinetic the energetically to cross enough transition states. disfavored themolecular dynamics computation. Model display will decrease the speedorder: in the following Wire Frame< Cylindrical Bonds < Ribbons< < Ball and Sticks< Sticks MolecularSur- dot surfaces < der Waals van Fill and Space

Administrator The total time of the run is the Step Interval times Figure 8.10: The Job Type tab the number of steps. Heating/Cooling Rate. dictates whether temperature adjustments are made. If the Heating/Cool- ing Rate check box is checked, the Heating/Cooling Rate slider determines the rate at which energy is added to or removed from the model when it is far from the target temperature. A heating/cooling rate of approximately 1.0 kcal/atom/picosecond results in small corrections which minimally disturb the trajectory. A much higher rate quickly heats up the model, but an equilibration or stabilization period is required to yield statistically meaningful results. To compute an isoenthalpic trajectory (constant Select the appropriate options: total energy), deselect Heating/Cooling Rate. Target Temperature. the final temperature to If you want to … Then Click … which the calculation will run. Energy is added to or removed from the model when the computed record each iteration Record Every Iteration. temperature varies more than 3% from the target as a frame in a movie temperature. for later replay The computed temperature used for this purpose is an exponentially weighted average temperature track a particular mea- Copy Measurements to with a memory half-life of about 20 steps. surement Output. Job Type Settings restrict movement of a Move Only Selected selected part of a Atoms. Use the Job Type tab to set options for the compu- model during the min- tation. imization

save a file containing Click Save Step Data In and the Time (in picosec- browse to choose a loca- onds), Total Energy, tion for storing this file. Potential Energy, and The word “heating” or Temperature data for “cooling” appears for each step. each step in which heating or cooling was performed. A summary of this data appears in the Message window each time a new frame is created.

Chem & Bio 3D 117 User Guide . distance for the box. olecular Dynamics olecular nformation a model of ttom of the Output win- C(2)-C(33) Selected tab and click the checkbox for checkbox the click tab and Job Type Job . Calculations>MM2>M The Steric EnergyThe Steric an the end of is computed at Run dow and examine the dow Copy Measurements to Output Copy Measurements molecule at 0.190 picoseconds. 0.190 picoseconds. molecule at When the calculation begins, the Output Window Output Window the When calculation begins, the appears. 5. Click (the active frame, if more than one exists). if more frame, (the active Figure C(2) - C(33) distance after calculation 8.12: Figure 13.7Å, Thedistance is approximately C(2)-C(33) 42% greater C(2)-C(33) distance. initial the than Compute Properties Compute Properties representspointa single energy computation that reportssteric the total energy for the currentco NOTE: MM2 Energyminimization. 4. the Click calculation before C(2) - C(33) distance 8.11: Figure Thebefore distance for the molecule C(2)-C(33) begancalculation the molecular dynamics is 9.4Å. approximately 6. to the bo Scroll down 3. Go to . in the Run . Stop key. . Thecompu- Enter Run . The dialog box Open king appearking in the Out- button on the dialog box button on the dialog box , the rightmost terminal carbon. and press the . . C(33) Save As , the leftmost terminal carbon, then toolbar. Structure>Measurements>Display Distance File>New Calculations>MM2>Run MM2 Job Calculations>MM2>Run C(2) F(C2F4)6F 118 Chapter 8 Measurement Shift+click Shift+click for the appropriate computation appears. A polymersegment consisting of six repeat units of tetrafluoroethylene appears in the model window. perform the computation: To 1. Select 3. Change and click parameters if desired Example: Computing the Molecular Dynamics Dynamics Molecular the Computing Example: of Segment Short a for Trajectory (PTFE) Polytetrafluoroethylene build the model: To 1. Go to Calculations Starting the Calculation Starting begin the computation, click To Messages iterationfortation each begins. and any are trac you measurements num- Thewhen the ends simulation put window. stop the steps To ber of specified is taken. computation before it is finished, click Saving a Job Saving if file JDF a in are saved and settings Thetype job the click you runthen can before runningYou a computation. session. work in a later these computations run MM2 job: previously created a To 1. Go to A measurement for the overall length of the mole- overall the A measurement for table. appears in the Measurement cule 2. Building tool. Select the Text 3. appears. A text box in the model window. Click 4. Type 2. Go to 2. and click Choose the file

Administrator A comparison of the steric energy of various con- The Output window appears. When the steric formations of a molecule gives you information on energy calculation is complete, the individual steric the relative stability of those conformations. energy terms and the total steric energy appear. Use the Output window scroll bar to view all of the NOTE: In cases where parameters are not available output. The units are kcal/mole for all terms. At because the atom types in your model are not among the the beginning of the computation the first message MM2 atom types supported, Chem3D will attempt an edu- indicates that the parameters are of Quality=4 cated guess. You can view the guessed parameters by using the meaning that they are experimentally deter- Show Used Parameters command after the analysis is com- mined/verified parameters. pleted. NOTE: The values of the energy terms shown here are approximate and can vary slightly based on the type of pro- Compare the steric energies of cis- and trans-2- cessor used to calculate them. butene. To build trans-2-butene and compute properties: The following values are displayed: 1. Go to File>New. 2. Select the Text Building tool. • Stretch represents the energy associated with 3. Click in the model window. A text box appears. distorting bonds from their optimal length. 4. Type trans-2-butene and press the Enter key. • Bend represents the energy associated with deforming bond angles from their optimal val- A molecule of trans-2-butene appears in the model ues. window. • Stretch-Bend term represents the energy 5. Go to Calculations>MM2>Compute Properties. The required to stretch the two bonds involved in a Compute Properties dialog box appears. bond angle when that bond angle is severely Figure 8.13: The Compute Properties dialog box compressed. • Torsion term represents the energy associated with deforming torsional angles in the molecule from their ideal values. • Non-1,4 van der Waals term represents the energy for the through-space interaction between pairs of atoms that are separated by more than three atoms. For example, in trans-2-butene, the Non-1,4 van der Waals energy term includes the energy for the interaction of a hydrogen atom bonded to C(1) with a hydrogen atom bonded to C(4). • 1,4 van der Waals represents the energy for the through-space interaction of atoms sepa- 6. Click Run. rated by two atoms. For example, in trans-2- butene, the 1,4 van der Waals energy term

Chem & Bio 3D 119 User Guide -2- trans -2- cis cis-2-butene (kcal/mol) Calcula- -2-butene is -2-butene has a . The parameters trans trans -2-butene are in the -2-butene are in the have values of 123.9°, values have parameters are rated as -2-butene. cis trans -0.0193 0.3794 butene (kcal/mol) and cis Energy TermEnergy trans-2- torsionder non-1,4 van Waals -1.4369Waals der 1,4 van 1.1742dipole/dipole -1.5366 total 0.0767 1.1621 0.1032 0.137 1.5512 much closer to the optimal value of 122.0°. The122.0°. of closer to the optimal value much terms for der Waals Non-1,4 van Bend and therefore butene are smaller, energy steric lower than butene because the C(1)-C(2)-C(3) and the C(2)- C(3)-C(4) bondhad angles to be deformed from 122.0°to 127.4° to relieve of optimal value their the interaction of from crowding of the steric some on C(1) and C(4). The interaction of hydrogens of C(4) C(1) and on hydrogens thus the C(1)-C(2)-C(3) less intense, and the much C(2)-C(3)-C(4) bond angles Bend and Non-1,4 van der Waals steric energy steric der Waals Non-1,4 van Bend and Theterms. term Bend higher in much is tions>MM2>Show Used Parameters appear inappear the Output window. Showing Used Parameters all parame- in the Output window display can You ters used in an MM2calculation. The list includes a Highest parameter. each of assessment quality quality empirically-derived of 1 indicates that a quality rating lowest 4 while a is a “best guess” value. parameter go to the used parameters, show To The significant differences between the steric The between differences significant energy terms for . The key. cis-2-butene (kcal/mol) Enter -2-butene, the -2-butene, -2-butene. trans -2-butene appears in -2-butene appears trans in cis

, butene (kcal/mol) and press the to delete the model. -2-butene appears in the model -2-butene button. cis -2-butene and compute properties:-2-butene and compute -2-butene and Run cis cis Calculations>MM2>Compute Properties Calculations>MM2>Compute Edit>Clear The values of theenergy The values terms shown here are cis-2-butene energywith the interaction associated bond of example For dipoles. includes the energyincludes a of interaction for the bondedatomhydro- with a to C(1) hydrogen gen to C(2). atom bonded Dipole/Dipole termDipole/Dipole includes the energy for C Alkane/C Alkene two the interactionthe of bond dipoles. 120 Chapter 8 steric energy terms for the Output window. appears. • The energy Dipole/Dipole steric represents the stretchbendstretch-bend 0.0627 0.0163 0.2638 0.0839 0.0435 1.3235 Energy Term trans-2- 5. the Click Below is a comparison of the steric energycomparison of the steric is a Below components for cessor used to calculate them. NOTE: 2. A text box in the model window. Double-click 3. Type A molecule of window. 4. Go to vary and can approximate slightlythe type of pro- based on To build build a To 1. Go to

Administrator Defining Atom Types 3. Enter the appropriate data in each field of the table. Be sure that the name for the parameter is To add an atom type to the Atom Types table: not duplicated elsewhere in the table. 1. Go to View>Parameter Tables>Atom Types. The 4. Close and Save the table. Atom Types table opens in a window. Repeating a Computation 2. To edit an atom type, click in the cell that you want to change and type new information. 1. Go to Calculations>MM2>Repeat MM2 Job. 2. Change parameters if desired and click Run. The computation proceeds.

Chem & Bio 3D 121 User Guide 122 Chapter 8

Administrator Chapter 9: Gaussian

Gaussian is a powerful, command-line driven, Predicting Spectra computational chemistry application including both ab initio and semi-empirical methods. It is not Using Gaussian, Chem & Bio 3D can predict included in Chem3D (the Gaussian menu option NMR, IR/Raman, and UV/VIS spectra. To calcu- appears gray), but can be purchased directly from late a spectrum, go to Calculations>Gaussian Interface CambridgeSoft. and select the spectrum you want. Chem3D 11 provides an interface for Gaussian calculations. The model in the Chem3D window NOTE: Depending on your computer’s speed and memory, transparently provides the data for creating Gauss- and the size of the model, Gaussian calculations may take ian jobs or running Gaussian calculations. Version several minutes. 11.0 supports all Gaussian calculations, offering the following features:

• 13C and 1H NMR spectra predictions TIP: Run a minimization before predicting spectra. MM2 • IR and Raman spectra predictions is faster than Gaussian minimization, and is usually ade- • Multi-step Jobs quate. Gaussian may fail to produce a spectrum if the model • Partial Optimizations is not at a minimum energy state. • Support for DFT Methods • Advanced Mode Viewing Spectra For information on how to use Gaussian, see the To view the predicted spectra, Go to View>Spec- documentation supplied with the Gaussian applica- trum Viewer. For each prediction that you run on a tion. given compound, a new tab will open in the Spec- trum Viewer. The Gaussian Interface The Gaussian interface offers several Gaussian features, including prediction of NMR, UV, IR, and Raman spectra.

Chem & Bio 3D 123 User Guide Chapter 9 Chapter , and select the , and l limit to the number of l limit to the number unselected portion, which- ssian interface Calculations>Gau job you want. job you to add a new job tomenu drop-down the queue. “-” the button. select the Link tab and click runs at use the any stop time, button ( toolbar. the Calculations ) on to either the selected or is more convenient. ever 2. Type the Job the “+” button, and use Click 3. queue, the a job from to remove want If you 1.wish to terminate If you the job queue. the Run jobs that can be linked. To run jobs: multiple To linked. be jobs thatcan 1. Go Minimization). first job (usually Select your Multi-step Jobs link jobs and runcan com- single them with a You mand. There is no technica Partial Optimizations perform a partial optimization: To 1.optimize may a portion Select of the model. You Figure 9.1: Predicted spectra for chlorobenzene for chlorobenzene spectra 9.1: Predicted Figure 124

Administrator 2. Select optimization from the Gaussian Interface Figure 9.3: Advanced Mode submenu. In the Gaussian Interface dialog box, click the Internal Coordinates radio button. 3. In the Move Which text window, indicate whether the selected or unselected atoms are to be optimized. Figure 9.2: Setting up a partial optimization

Internal coordinates Note the Gaussian 2003 Keywords link under the text window. If you need help, clicking the link opens your web browser to the keywords page of the Gaussian Web site. Support for DFT Methods Selecting DFT for Method opens a dialog box Input Template where you can choose which DFT method you The General tab of the Gaussian Interface dialog wish to use. box contains the input template. You can set out- Figure 9.4: DFT methods put parameters with the checkboxes and edit keywords in the run file. Advanced Mode If you are an expert user, you can go directly to a text entry window similar to the input template. Just click Use Advanced Mode on the Gaussian Interface submenu.

When you have chosen a method, the complete DFT method information is displayed, and a button appears next to the Method text box to allow you to edit your input.

Chem & Bio 3D 125 User Guide Chapter 9 Chapter tab, or set or set tab, tab. See the tab. Jobs ) ) CalcAll Advanced CalcFC Options are: Options are: Selects a solvation model. See model. See Selects a solvation Selects closed or open shell. See shell. See closed or open Selects Specifies a polarization function for tab displays parameters that are parameters displays tab Sets defaultscom- different types of for Most methods set. basis Specifies the Selects a method. Adds a diffuse function tofunction the basis set. If diffuse Adds a If you select a solvation model, you may may model, you a solvation select If you Advanced If you selected a Polarization function, you function, you a Polarization selected you If your own parameters. parameters. own your • No calculation •( Initial force constants •point ( at each Calculate • None—no options •for all orbitals but Regular, as Full—same Population Analysis. Population Job Type. Type. Job putations. Method. Basis Set. set be specified. See the Gaussian basis require a for exceptions. Help file Wave Function. Configuration” on page“Specifying the Electronic 241 for more details. Polarization. or heavier). S, (P, atoms heavy H. anshould also H choose function. Diffuse. should also use specify a diffuse function, you you on the Tight Convergence 2. on the the defaults use may You adjusted less often. Only those parameters thatless often. Only those parameters adjusted selected are active. have applyjobthe to type you are: they minimizations, For Model. Solvation for in the Gaussian manual the SCRF keyword informationmethods. on Solvent. for all models Thesolvent default solvent. select a is water. Constants. Force Gaussian manual for details. manual Gaussian The ). The Gaussian dialog Interface Calculations>Gaussian Interface>Minimize Interface>Minimize Calculations>Gaussian (Energy/Geometry box appears, with Minimize as the default Job as the default Job with Minimize appears, box Type. Figure 9.6Gaussian menu Figure Minimizing Energy Minimizing energy is generally the first molecular may performedcomputation on You a model. minimize all or part of are minimiz- a model. If you selec- your ing part should make model, you of a before to include or exclude tion of what on page See “Other Options” 127. continuing. 1. Go to Figure 9.5: DFT display 9.5: DFT Figure 126

Administrator • Minimum—outputs the total atomic charges as possible. Do not use a local or global minimum, and orbital energies because the algorithm cannot effectively move the • Regular — outputs five highest occupied and geometry from that starting point. five lowest virtual orbitals, with density matri- To optimize a transition state: ces and full Mulliken population analysis 1. Go to Calculations>Gaussian Interface>Optimize to Other Options Transition State. The Gaussian Interface dialog box appears. By default, Gaussian uses modest convergence cri- Figure 9.7: Optimizing to a transition state teria to speed up calculations. The Use Tight Conver- gence checkbox adds the keyword “tight” to the input template to specify full convergence. You may also add a charge by first deselecting the default Use Formal Charge checkbox, or change the Spin Multiplicity. Spins can be positive integers. Charges may be plus or minus. Selecting the Internal Coordinate radio button allows you to minimize only part of the model by choosing either Selected Atoms or Unselected Atoms. On the General Tab, set the parameters that control the output: Display Every Iteration. Displays the minimization process “live” at each iteration in the calculation.

NOTE: Adds significantly to the time required to minimize the structure.

2. You may use the defaults, or set your own Show Output in Notepad. Sends the output to a parameters. text file. Send Back Output. Displays the value of each NOTE: Unless you are an experienced Gaussian user, use measurement in the Output window. the Transition State defaults.

NOTE: Adds significantly to the time required to mini- 3. On the Properties tab, select the properties you mize the structure. wish to calculate from the final optimized conformation. Optimize to Transition State 4. On the General tab, type any additional keywords that you want to use to modify the optimization. To optimize your model to a transition state, use a conformation that is as close to the transition state 5. Click Run.

Chem & Bio 3D 127 User Guide Chapter 9 Chapter terface > Create Input terface > Interface>Run Input Input Interface>Run Show Output in Notepad Output in Show Output Send Back . Calculations Gaussian In Calculation Run The Run Gaussian Input file dialog box Gaussian Input file dialog box TheRun . File appears. to location. File. If you want to … to you want If … click Then the output to a save file. in the results display the Outputwindow 2. the full the Gaussian file or Browse path of Type 3. Select the appropriate options. 4. Click The a certain At input file runs. point,new a tab Win- opens and the model appears in the Model dow. Running a Gaussian Job select a previ- to Chem & Bio 3D 11.0 enables you ously created Gaussian(JDF). job description file The JDF file can be thought of as a set of Settings that apply to a particular dialog box. to select a previously created Chem3D enables you Gaussian job description file (JDF). The JDF file 3. Create. Click File Running an Input Gaussian GJF a previously created have If you run can you file from within the input file, Chem3D. run a input file: Gaussian To 1. Go to puter. You must have Gaussian installed to create to installed Gaussian have must You puter. file. an input 1.create a model. Open or 2. Go to . format intended to

within the dialog box within the dialog box tton is deactivated in the deactivated tton is Save button. Run Calculations >Gaussian>Compute Properties >Gaussian>Compute Calculations The Gaussian Interface dialog box appears, with appears, The dialog Gaussian Interface box the Properties tab selected. 2. Select the properties to estimate. 3. the Click saves modifications without the appearance of a without the appearance of modifications saves warning or confirmation box. dialog either format Saving the Gaussian Job within for conve- folder adds it to the Gaussian submenu nient access. files; they Preferences like are description files Job save may You ofdialog the store the settings box. modify You JDT type. or a the file as either a JDF JDF files more easily than JDT files. save and You can create a Gaussian input file and run it You to run want Thisif you becomes useful the later. calculation more than once or on a different com- Creating an Input File Creating dialog box of a template file. of dialog box JDF Format Theformat JDF formata file is job for saving Clicking descriptions. JDT Format Theformat JDT a template is servetypes other job from which as a foundation The Minimize Energy be derived. and Com- may pute Propertiessuppliedjob Chem3D with types discourage modification To are examples of these. bu the Save of these files, Job Description File Formats Job Description they files; Preferences like are description files Job There are two of the dialog box. store the settings types as described below. To specify the parameters for calculations to pre- parameters for calculations specify the To dict properties of a model: 1.to Go Computing Properties Computing 128

Administrator can be thought of as a set of Settings that apply to Compute Properties, and so on.) saved within a particular dialog box. the file appears. You can create a JDF file from the dialog box of 3. Click Run. any of the Gaussian calculations (Minimize Energy, Optimize to Transition State) by clicking Save As Repeating a Gaussian Job after all Settings for the calculation have been set. After you perform a Gaussian calculation, you can For more information about JDF files see “Job repeat the job as follows: Description File Formats” on page 128. 1. From the Gaussian submenu, choose Repeat [name To run a Gaussian job: of computation]. The appropriate dialog box 1. From the Gaussian submenu, choose Run Gauss- appears. ian Job. The Open dialog box appears. 2. Change parameters if desired and click Run. The 2. Select the file to run. The dialog box corre- computation proceeds. sponding to the type of job (Minimize Energy,

Chem & Bio 3D 129 User Guide Chapter 9 Chapter 130

Administrator Chapter 10: MOPAC Calculations

MOPAC is a molecular computation application • Computing Properties that features a number of widely-used, semi-empir- •Examples ical methods. CambridgeSoft makes it available in two versions, Professional and Ultra. • Locating the Eclipsed Transition State of CS MOPAC provides a graphical user interface Ethane that allows you to perform MOPAC computations • Example 1: Dipole Moment directly on the model in the Chem3D model win- • Example 2: Cation Stability dow. As a computation progresses, the model • Example 3: Charge Distribution changes appearance to reflect the computed result. • Example 4: The Dipole Moment of m- MOPAC Pro allows you to compute properties Nitrotoluene and perform simple (and some advanced) energy minimizations, optimize to transition states, and • Example 5: Phase Stability compute properties. The CS MOPAC Pro imple- • Example 6: Hyperfine Coupling Constants mentation supports MOPAC sparkles, has an • Example 8: RHF Spin Density improved user interface, and provides faster calculations. It is included in some versions of Chem3D, • Using MOPAC Properties or may be purchased from CambridgeSoft as an • Using MOPAC files optional plug-in. The procedures assume you have a basic under- MOPAC Ultra is the full MOPAC implementa- standing of the computational concepts and termi- tion, and is only available as an optional plug-in. CS nology of semi-empirical methods, and the MOPAC Ultra provides support for previously concepts involved in geometry optimization (mini- unavailable features such as MOZYME and PM5 mization) and single-point computations. methods. To install either version of MOPAC, Chem & Bio Minimizing Energy 3D 11.0 must be installed first. Either version of Minimizing energy is generally the first molecular MOPAC will work with either version of Chem3D. computation performed on a model. Go to Calcu- In this section: lations>MOPAC Interface>Minimize Energy. The • Minimizing Energy MOPAC Interface dialog box appears, with Mini- mize as the default Job Type. • Optimizing Geometry • Optimizing to a Transition State

Chem & Bio 3D 131 User Guide partselecting of a model by it. criteria for the gradient of the potential energy sur- (See also “Gradient face. Norm” on page 137.) very large models, For SCF is the alters the way generated,memory cutting runningrequirements and much faster. the Displays minimization itera- at each “live” process tion in the calculation. Adds significantly to the time required to minimize the structure. Sends the output to a text file. measurement in the Output window. Adds significantly to the time required to minimize the structure. —The default value of 0.100 is a reasonable 0.100 is of —The default value Option WhichMove Function minimize to you Allows RMSMinimum convergence the Specifies Use MOZYME Every Display Itera- tion Output in Show Notepad Output Send Back each of the value Displays compromise between accuracy and speed. Reduc- between compromise that the calculation continues means value the ing longer closer to a minimum. it tries to getas even shortens the calculation, but Increasing the value farther the Increase you from a minimum. leaves Notes RMS Ultra only types of computations. the Elec- “Specifying See tronic Configuration” on page details. 241 for more See “Optimizing mizer. Geometry” on page 133 for more information. information on solvent see the online effects, manual. MOPAC 132 Chapter 10 Option TypeJob Method Function defaults for different Sets FunctionWave open shell. or close Selects Selects a method. Optimizer Selects a geometry mini- Solvent more For Selects a solvent. You may use the defaults, or set your own parame- own your or set use the defaults, may You ters. Figure 10.1: The MOPAC Interface dialog Interface box 10.1: The MOPAC Figure

Administrator value if you want a better optimization of a confor- TS mation that you know is not a minimum, but you The TS optimizer is used to optimize a transition want to isolate it for computing comparative data. state. It is inserted automatically when you select If you want to use a value <0.01, you must specify Optimize to Transition State from the MOPAC Interface LET in the keywords section (General Tab). submenu. Wave Function—Selecting a wave function from the drop down menu involves deciding whether to BFGS use RHF or UHF computations. For large models (over about 500-1,000 atoms) the RHF is the default Hartree-Fock method used for suggested optimizer is the Broyden-Fletcher-Gold- closed shell systems. To use RHF select the Close farb-Shanno procedure. By specifying BFGS, this Shell (Restricted) wave function. procedure will be used instead of EF. UHF is an alternative form of the HF method LBFGS used for open shell systems. To use UHF select the For very large systems, the LBFGS optimizer is Open Shell (Unrestricted) wave function. If you wish often the only method that can be used. It is based to calculate Hyperfine Coupling Constants, you on the BFGS optimizer, but calculates the inverse must select the UHF wave function. Hessian as needed rather than storing it. Because it uses little memory, it is preferred for optimizing NOTE: UHF computations take at least twice as long as very large systems. It is, however, not as efficient as RHF. This may be the deciding consideration of method the other optimizers. when large molecules are being studied. Adding Keywords Click the General tab to specify additional MOPAC Optimizing Geometry keywords. This will tailor a calculation to more exacting requirements. For example, you might use Chem3D uses the Eigenvector Following (EF) additional keywords to control convergence crite- routine as the default geometry optimization rou- ria, to optimize to an excited state instead of the tine for minimization calculations. EF is generally ground state, or to calculate additional properties. superior to the other minimizers, and is the default used by MOPAC 2002. (Earlier versions of MOPAC used BFGS as the default.) The other NOTE: Other properties that you might specify through the alternatives are described below. keywords section of the dialog box may affect the outcome. For more information see “Using Keywords” on page 240.

Chem & Bio 3D 133 User Guide and Method , the Output window , the Output window tab select a tab, select the properties you tab, tab, type any additional keywords type any additional keywords tab, . . The. information about the model and Send Back Output Job and Theory and Job Properties General Unless you are an experienced MOPAC user, use user, areUnless you an experienced MOPAC Run the keywords are sent to MOPAC. If you have have you If to MOPAC. are sent the keywords selected Wave Function Wave from the final optimized con- wish to calculate formation. to use to the modify want optimization. that you appears. appears. 4. On the 5. Click 2. On the NOTE: defaults. State Transition the 3. On the intermediateThe displays Output window mes- sagesabout the statusthe minimization. of mes- A sage terminatesminimization the appears if a poorto starting due usually confor- abnormally, mation. Figure 10.3: Optimizing to a transition to a Optimizing state 10.3: transition Figure . The MOPAC Interface dialog The. MOPAC Calculations>MOPAC Interface>Optimize to Interface>Optimize Calculations>MOPAC 134 Chapter 10 box appears. appears. box Transition State Transition To optimize your model to a use a transition your optimize state, To conformationtransitionstate asto the close that is Do not use a local or global minimum, as possible. the because the algorithm move cannot effectively geometry from that starting point. optimize a transition state: To 1. Go to Optimize to Transition State Optimize to Transition Figure 10.2: tab The General 10.2: Figure

Administrator The following contains keywords automatically For descriptions of error messages reported by sent to MOPAC and some additional keywords you MOPAC see Chapter 11, pages 325–331, in the can use to affect convergence. MOPAC manual. To interrupt a minimization that is in progress, Keyword Description click Stop.

EF Automatically sent to MOPAC Locating the Eclipsed Transition State of to specify the use of the Eigen- Ethane vector Following minimizer. Build a model of ethane: GEO-OK Automatically sent to MOPAC 1. Go to File>New. to override checking of the 2. Double-click in the model window. A text box Z-matrix. appears. 3. Type CH3CH3 and press the Enter key. A model MMOK Automatically sent to MOPAC to specify Molecular Mechan- of ethane appears. ics correction for amide bonds. 4. Select the Rotation tool. Use the additional keyword 5. Click the arrow next to the Rotation tool, and NOMM to turn this keyword drag down the Rotation dial. off. Figure 10.4: The Rotation dial RMAX=n.nn The maximum for the ratio of calculated/predicted energy click here to open the Rotation dial change. The default is 4.0.

RMIN=n.nn The minimum for the ratio of calculated/predicted energy dihedral rotators change. The default value is 0.000. 6. Hold down the S key and select the bond PRECISE Runs the SCF calculations between the C(1) and C(2) atoms. using a higher precision so that values do not fluctuate from NOTE: Holding down the S key temporarily activates the run to run. Select tool. LET Overrides safety checks to make the job run faster (or fur- 7. Select one of the dihedral rotators, then enter 57 ther). in the text box and press the Enter key. A nearly RECALC=5 Use this keyword if the optimi- eclipsed conformation of ethane is displayed. zation has trouble converging to a transition state. TIP: To view this better, rotate the model on the Y axis until the carbon atoms are aligned.

Chem & Bio 3D 135 User Guide . charges f H Δ tab, select the properties cal- to tab, set the tab, tab, type any additional keywords, type any additional keywords, tab, tab, choose a potential energypotential a choose tab, . Theory Properties Properties General The heat of formation include the zero values point Run function performing to use for calculation. the culate. if necessary. if necessary. 2. On the 3. On the 6. Click 5. On the MOPAC Properties MOPAC The section describes the properties following that conformation can for calculate a you given of your model, either as a single point energy computation using the Compute Propertiesa after command, or minimization using either the Minimize Energy or State commands. Optimize to Transition Heat of Formation, This energy represents the heat value of formation current conformation.model’s It is usefulfor for a comparing the stabilityof conformations the of same model. NOTE: point energy is found at the bottom of the *.out file. Figure 10.5: The Properties tab Properties The 10.5: Figure 4. the On energies. To obtain the zeroenergies. point energy To for a conformation The zero-run FORCE. a force operation using the keyword box on box . tab. . The and appears Measurement table The Compute Properties dialog box Copy Measurements to Messages Copy . The. ethane model minimizes so that . Calculations>MOPAC Interface>Compute Interface>Compute Calculations>MOPAC View>View Position>Align View Z Axis With With Axis Z View Position>Align View>View Calculations>MOPAC Interface>Optimize to Interface>Optimize Calculations>MOPAC Structure>Measurements>Generate All Dihe- If you performyou EnergyIf an from Minimization the Run Job Type 136 Chapter 10 appears. Properties. Selection Transition State Transition dral Angles dihedral for the selected actual value an displays angle 3 degrees of about (this willvary slightly experiments).between the the dihedral corresponding is 0 degrees, to the eclipsed conformation tran- a known of ethane, the staggeredsition state between con- minima formations. two nearly eclipsed hydrogen atoms, such as such atoms, eclipsed nearly hydrogen two track. H(7), to identify the dihedral to H(4) and a nearly coplanar four-atom have should You as H(4)-C(1)-C(2)-H(7), selected. such chain, 3. Go to To see the Newman projection of the eclipsed projection see the Newman To ethane model: 1. carbon atoms. both Select 2. Go to Computing Properties perform a single point calculation on the cur- To rent conformationof a model: 1. Go to NOTE: instead of optimizing degrees, state. to the transition Use MOPAC to create the precise eclipsed transi- eclipsed precise to create the MOPAC Use tion state: 1. on any click keys, the S and shift down Holding 2. Go to 4. the Click 5. Click same starting dihedral, your model wouldmodel same starting optimize your dihedral, to the staggered conformationdihedral60 where of ethane the is

Administrator The heat of formation in MOPAC is the gas-phase mum geometry the model is for the particular heat of formation at 298K of one mole of a com- calculation. pound from its elements in their standard state. The heat of formation is composed of the follow- NOTE: The GNORM property is not the same as the ing terms: MOPAC keyword GNORM. For more information see the MOPAC manual, pages 31 and 180. ΔΗ f =Εelec+Εnucl +Εisol +Εatom

Where: Dipole Moment •Eelec is calculated from the SCF calculation. The dipole moment is the first derivative of the energy with respect to an applied electric field. It •Enucl is the core-core repulsion based on the nuclei in the molecule. measures the asymmetry in the molecular charge distribution and is reported as a vector in three •Eisol and Eatoms are parameters supplied by the dimensions. potential function for the elements within your The dipole value will differ when you choose Mul- molecule. liken Charges, Wang-Ford Charges or Electrostatic Potential, as a different density matrix is used in NOTE: You can use the keyword ENPART and open the each computation. *.out file at the end of a run to view the energy components making up the heat of formation and SCF calculations. See NOTE: For more information see the MOPAC manual, the MOPAC online manual reference page 137, for more page 119. information.

The following table contains the keywords auto- Gradient Norm matically sent to MOPAC This is the value of the scalar of the vector of Charges derivatives with respect to the geometric variables The property, Charges, determines the atomic flagged for optimization. This property (called charges using a variety of techniques discussed in GNORM in the MOPAC manual) is automatically the following sections. In this example the charges selected for a minimization, which calculates the are the electrostatic potential derived charges from GNORM and compares it to the selected mini- Wang-Ford, because Wang-Ford charges give use- mum gradient. When the selected minimum is ful information about chemical stability (reactivity). reached, the minimization terminates. Selecting this property for a Compute Properties Mulliken Charges operation (where a minimization is not being per- This property provides a set of charges on an atom formed) will give you an idea of how close to opti- basis derived by reworking the density matrix from the SCF calculation. Unlike the Wang-Ford charges used in the previous example, Mulliken charges

Chem & Bio 3D 137 User Guide Automatically sent to MOPAC to sent to MOPAC Automatically specify the generation of Point Charges from PMEP. to sent to MOPAC Automatically electro- the Wang/Ford specify routine. static Potential to sent to MOPAC Automatically of the Z-matrix. checking override to sent to MOPAC Automatically cor- Mechanics specify Molecular Use the rection for amide bonds. to NOMM additional keyword off. turn this keyword For elements not covered elements not potential by the AM1 For Keyword Description PMEP QPMEP GEO-OK MMOK Electrostatic Potential Electrostatic electrostatic potential propertythe Use when the function potential of the AM1 element coverage For not apply to the molecule of interest. does online manual, more information see the MOPAC page 223. Wang-Ford Charges Wang-Ford This computation of point charges can be used only. potential function with the AM1 NOTE: lar informationpropertiesoutside this on elements range. automatically sent to are the keywords Below MOPAC. There are two properties available for calculating for calculating properties available Theretwo are Charges and pointatomic charges: Wang-Ford Potential. Electrostatic the Electrostatic property function, use Potential simi- get to Automatically sent to MOPAC to sent to MOPAC Automatically generate Population the Mulliken Analysis. to sent to MOPAC Automatically of the Z-matrix. checking override to sent to MOPAC Automatically cor- Mechanics specify Molecular the Use rectionamide for bonds. to NOMM additional keyword off. turn this keyword For more information, see the MOPAC online more information,seethe MOPAC For 138 Chapter 10 GEO-OK MMOK Keyword Description MULLIK Electrostatic Potential from an electrostatic potential The charges derived useful information about chemi- give computation cal reactivity. creating The electrostatic potential is computed by an electrostatic potential grid. Chem3D reports the grid. a such from derived charges point a better In general, these atomic point charges give when compared attack sites of indication of likely from the Coulson den- to atomic charges derived sity matrix population (Charges) analy- Mulliken or Charges).The (Mulliken sis uses for electrostatic charges are generally the same as potential derived see “Charges” examples, For for atomic charges. on page 137. NOTE: manual, page 41 and 121. auto- the keywords table contains The following matically sent to MOPAC. give a quick survey of chargea quick a mol- in distribution give ecule.

Administrator The following table contains the keywords auto- zz, xz, yz, xy), second-order (beta) tensors and matically sent to MOPAC and those you can use to third order (gamma) tensors. affect this property. NOTE: Polarizabilities cannot be calculated using the Keyword Description MINDO/3 potential function.

ESP Automatically sent to MOPAC to specify the Electrostatic Potential COSMO Solvation in Water routine. The COSMO method is useful for determining the stability of various species in a solvent. The default POTWRT Add this keyword if you want to solvent is water. For more information, see the print out the ESP map values. MOPAC online manual. GEO-OK Automatically sent to MOPAC to To run the COSMO method, make the following override checking of the Z-matrix. selections in the MOPAC Interface:

MMOK Automatically sent to MOPAC to • On the Job & Theory tab, select COSMO in specify Molecular Mechanics cor- the Solvent field. rection for amide bonds. Use the • On the Properties tab, check the COSMO Area additional keyword NOMM to and/or COSMO Volume properties. You must turn this keyword off. check each property you want to see in the results. Molecular Surfaces Molecular surfaces calculate the data necessary to NOTE: You can also use the Miertus-Scirocco-Tomasi sol- render the Total Charge Density, Molecular Elec- vation model, which is available using the H2O keyword. trostatic Potential, Spin Density, and Molecular This method is recommended only for water as the solvent. A Orbitals surfaces. discussion of this method can be found in the MOPAC Polarizability online documentation. The polarizability (and hyperpolarizability) property provides information about the distribution of Hyperfine Coupling Constants electrons based on presence of an applied electric field. In general, molecules with more delocalized Hyperfine Coupling Constants are useful for simu- electrons have higher values for this property. lating Electron Spin Resonance (ESR) spectra. Polarizability data is often used in other equations Hyperfine interaction of the unpaired electron with for evaluation of optical properties of molecules. the central proton and other equivalent protons For more information see the MOPAC online cause complex splitting patterns in ESR spectra. manual, page 214. ESR spectroscopy measures the absorption of microwave radiation by an unpaired electron when The polarizability and hyperpolarizability values it is placed under a strong magnetic field. reported are the first-order (alpha) tensors (xx, yy, Hyperfine Coupling Constants (HFCs) are related to the line spacing within the hyperfine pattern of an ESR spectra and the distance between peaks.

Chem & Bio 3D 139 User Guide rons are computed. For rons are computed. For Automatically sent to MOPAC to sent to MOPAC Automatically of the Z-matrix. checking override to sent to MOPAC Automatically cor- Molecular Mechanics specify the Use rection for amide bonds. to NOMM additional keyword off. turn this keyword to print keyword can add this You *.out the spin density matrix in the file. Automatically sent to MOPAC if sent to MOPAC Automatically “Open Shell (Unre- choose you functions to specify stricted)” wave the use of the Unrestricted Har- methods. tree-Fock GEO-OK MMOK SPIN Keyword Description UHF RHF Spin Density uses the 1/2 electron RHF Spin Density correction and a single configuration interaction calculation to This spin density in a molecule. isolate the alpha particularlymethod is useful when the UHF Spin too resource inten- becomes Density computation more information see For for large molecules. sive pageonline manual, 28. the MOPAC UHF Spin Density UHF Spin closed shell the TheDensity removes UHF Spin functions for separate wave restriction.so, In doing and beta spin elect alpha online manual, more information see the MOPAC page 152. auto- contains the keywords table The following can use to and those you matically sent to MOPAC affect this property. Two of methods spin density calculating of mole- Two RHF with cules unpaired available: are electrons Density. UHF Spin and Spin Density Automatically sent to MOPAC to sent to MOPAC Automatically Z-matrix. of the checking override to sent to MOPAC Automatically cor- Mechanics specify Molecular Use the for amide bonds. rection to NOMM additional keyword off. turn this keyword Automatically sent to MOPAC if sent to MOPAC Automatically “Open Shell (Unre- choose you functions to spec- wave stricted)” Unrestricted the ify the use of methods. Hartree-Fock to sent to MOPAC Automatically computation. specify the hyperfine 140 Chapter 10 • radicals Free • molecules electron Odd •complexes metal Transition • Rare-earth ions • molecules Triplet-state MMOK Hyperfine GEO-OK Keyword Description UHF Spin Density molecules where there is an in arises Spin density rela- provides Spin density data unpaired electron. alphafor a particu- spin electrons amounts of tive lar state. is a useful property sites Spin density accessing for spectra. ESR and for simulating reactivity of For more information see the MOPAC online more informationFor see the MOPAC pagemanual, 34. auto- the keywords table contains The following can to use and those you matically sent to MOPAC affect this property. Species that contain unpaired electrons are as fol- are electrons unpaired contain that Species lows:

Administrator The following table contains the keywords auto- 7. On the Properties tab, select Dipole. matically sent to MOPAC and those you can use to 8. Click Run. affect this property. The results shown in the Messages window indicate the electron distribution is skewed in the Keyword Description direction of the oxygen atom.

ESR Automatically sent to MOPAC to X Y Z Total specify RHF spin density calculation. Dipole -2.317 0.000 0.000 2.317 (vector Debye) GEO-OK Automatically sent to MOPAC to If you rotate your model, the X,Y, and Z compo- override checking of the Z-matrix. nents of the dipole differ. However, the total dipole does not. In this example, the model is oriented so MMOK Automatically sent to MOPAC to that the significant component of the dipole lies specify Molecular Mechanics cor- along the X-axis. rection for amide bonds. Use the additional keyword NOMM to Example 2: Cation Stability turn this keyword off. This example compares cation stabilities in a homologous series of molecules. Example 1: Dipole Moment To build the model: This example describes how to calculate the dipole moment for formaldehyde: 1. Go to File>New. 2. Click the Text Building tool. 1. Go to File>New Model. 3. Click in the model window. A text box appears. 2. Click the Text tool. 4. For tri-chloro, type CCl3 and press the Enter key. 3. Click in the model window. A text box appears. 5. Repeat step 1 through step 4 for the other cat- 4. Type H2CO and press the Enter key. A model of ions: type CHCl2 for di-chloro; type CH2Cl for formaldehyde appears. mono-chloro and CH3 for methyl cation. Figure 10.6: Formaldehyde model

NOTE: The cations in this example are even electron closed shell systems and are assumed to have Singlet ground state. No modifications through additional keywords are necessary. The default RHF computation is used.

6. For each model, click the central carbon, type “+” and press the Enter key. The model changes to a cation and insures that the charge is sent to MOPAC. 5. Go to Calculations>MOPAC Interface>Minimize To perform the computation: Energy. 6. On the Theory tab, choose AM1. 1. Go to Calculations>MOPAC Interface>Minimize Energy.

Chem & Bio 3D 141 User Guide at the key. key. group

Enter . . This automati- nitro PM3 Charges Interface>Minimize Interface>Minimize from the Charges list. , then press the NO2 tool. Mulliken , type Text . Calculations>MOPAC Calculations>MOPAC All the monosubstituted phenols under examina-All the monosubstituted . Run H10 The para-nitrophenoxide ion displays. ion displays. The para-nitrophenoxide Energy cally selects Perform minimization as in the last step. monosubstituted nitro phenols, the last two For first,the nitro group select using the Select Tool the Add and press the Delete key. To build the para-nitrophenoxide ion: build the para-nitrophenoxide To 1. the Click 7. select On the Propertytab, 2. Click Figure 10.7: Phenoxide ion model ion Phenoxide 10.7: Figure NOTE: used. 5. Go to 6. choose On the Theorytab, 8. Click tion areeven electron closedshell and are systems assumed to groundhave modifications Singlet by additional state. No arekeywords necessary.is computation The default RHF meta (H9) or orthorepeat (H8) position and the analysis. shown are analyses The series of this data from The substitution of a nitro group at para, below. meta and orthodecrease in neg- a positions shows in the order oxygen at the phenoxy charge ative where orthosubstitution shows meta>para>ortho,

2 in the Prop- key. A phenoxide A phenoxide key. Charges AM1. Enter distributed to different . ility is tri-chloro >di- isility tri-chloro tool. from the Charges list. and press the and press Text Building Text . The results for the model appear in The . the model results for File>New Model Wang-Ford Run PhO- 142 Chapter 10 erties list. ion model appears. ion model the Message window when the computation is is when the computation the Messagewindow complete. 4. Select The molecules are now planar, reflectingsp planar, now Theare molecules 2. the Click In this example, we analyze the charge distribution we In this example, ions. ofin a series mono-substituted phenoxy 1. Go to Example 3: Charge Distribution Example 3: Charge hybridization of thehybridization central carbon. can reason you these simple computations, From thethat the chargethe cation of is not localized to but is rather central carbon, chargedthe to the other atoms attached extents by group cations of this The for general trend carbon. to the atoms attached that more chlorine the is charged the cation carbon, the more stable (the stab decreasing order of > methyl). > mono-chloro chloro 2. On the Theory choose tab, 3. select Properties On the tab, 5. Click 3. in the model window. Click 4. Type

Administrator the greatest reduction of negative charge on the phenoxy oxygen. You can reason from this data Phenoxide p-Nitro m- Nitro o-Nitro that the phenoxy ion is stabilized by nitro substitution at the ortho position. O14 - O14 - O14 - 0.70345 0.64406 0.65424 Phenoxide p-Nitro m- Nitro o-Nitro Example 4: The Dipole Moment of m- C1 0.39572 C1 C1 C1 Nitrotoluene 0.41546 0.38077 0.45789 Here is another example of calculating the dipole C2 -0.46113 C2 - C2 - C2 - moment of a model. This time, we use m-nitrotolu- 0.44929 0.36594 0.75764 ene: 1. Go to File>New. C3 -0.09388 C3 - C3 - C3 0.00519 0.33658 0.00316 2. Click the Text tool. 3. Click in the model window. A text box appears. C4 -0.44560 C4 - C4 - C4 - 4. Type PhCH3 and press the Enter key. A model of 0.71261 0.35950 0.41505 toluene appears. Reorient the model using the C5 -0.09385 C5 - C5 - C5 - Trackball tool until it is oriented like the model 0.00521 0.10939 0.09544 shown below. 5. Go to Edit>Select All. C6 -0.46109 C6 - C6 - C6 - 6. Go to View>Model Display>Show Serial Numbers. 0.44926 0.41451 0.38967

O7 -0.57746 O7 - O7 - O7 - NOTE: Show Serial Numbers is a toggle. When it is 0.49291 0.54186 0.48265 selected, the number 1 displays in a frame. H8 0.16946 H8 H8 N8 0.18718 0.21051 1.38805 7. With the Text Building tool, click H(11), then H9 0.12069 H9 N9 H9 type NO2 in the text box that appears. 0.17553 1.31296 0.16911 8. Press the Enter key. A model of m-nitrotoluene appears. H10 0.15700 N10 H10 H10 Figure 10.8: m-nitrotoluene model 1.38043 0.19979 0.17281 H11 0.12067 H11 H11 H11 0.17561 0.14096 0.13932 H12 0.16946 H12 H12 H12 0.18715 0.17948 0.18090 O13 - O13 - O13 - 0.70347 0.65265 0.71656

Use MOPAC to find the dipole moment:

Chem & Bio 3D 143 User Guide . key. A modelkey. . Heat of Formation COSMO Solvation Enter PM3 Interface>Minimize Interface>Minimize Interface>Minimize . Automatically sent to MOPAC sent to MOPAC Automatically Mechan- Molecular specify to ics correctionbonds. for amide keyword Use the additional turnNOMM to this keyword off. . and press the and press . TheMessagesthe in results appear . The. the Messagesappear in results Calculations>MOPAC Calculations>MOPAC Calculations>MOPAC File>New Run . . Run HGlyOH Energy Energy of glycine appears. window. and COSMO Solvation window. KeywordMMOK Description 9. Go to 7. Ctrl+click On the Property tab, 8. Click Figure 10.9: Glycine model model Glycine 10.9: Figure 5. Go to create the zwitterionic form: To Example 5: Phase Stability Example 5: Phase the the compare stability of we In this example, gas and Zwitterion in water phases. glycine compare stabilities: To 1. Go to 2.tool. the Text Click 3. appears. A text box in the model window. Click 4. Type 11.Click 11.Click 6. choose On the Theorytab, deselect 10.On the Property tab, . . AM1 Polarizabilities -nitrotoluene. -nitrotoluene. m Automatically sent to MOPAC sent to MOPAC Automatically rou- to specify the polarizablity n is the startingtine. voltage in is Thevalue default eV. E = 1.0. can reenter the keyword You for n to value and another change the startingvoltage. sent to MOPAC Automatically of the checking to override Z-matrix. . Calculations>MOPAC Interface>Minimize Interface>Minimize Calculations>MOPAC . Run 144 Chapter 10 Energy GEO-OK Keyword POLAR Description (E=(n1, n2, n3)) Applied field (eV) alpha xx0.000000 alphayy 108.234000.250000 alpha zz 97.70127 108.404800.500000 18.82380 97.82726 108.91847 18.83561 98.20891 18.86943 The following table contains the keywords auto- table contains the keywords The following can use to you and those matically sent to MOPAC affect this property. The results is a subset of the table show- following first the field on electric applied effect of an ing the for order polarizability 1. Go to 3. select the Property On tab, 2. On the Theory choose tab, 4. Click

Administrator 1. Click the Text tool. 5. Click the Select tool. 2. Click the nitrogen, type “+”, then press the Enter 6. Select H(8). key. 7. Press the Backspace key. 3. Click the oxygen atom, type “-”, then press the If you have automatic rectification on, a message Enter key. The glycine zwitterion is formed. appears asking to turn it off to perform this opera- Figure 10.10: Glycine zwitterion tion. 8. Click Turn Off Automatic Rectification. The Ethyl Radical is displayed. Figure 10.11: Ethyl radical model

4. Perform a minimization with and without the COSMO solvation property selected as performed for the glycine model. The following table summarizes the results of the four analyses.

Form of glycine ΔH Solvent (kcal/mole) Accessible Surface Å2 To perform the HFC computation: neutral (H2O) -108.32861 52.36067 1. Go to Calculations>MOPAC Interface >Minimize zwitterion (H2O) -126.93974 52.37133 Energy. neutral (gas) -92.75386 2. On the Theory tab, choose the PM3 potential function and the Open Shell (Unrestricted) wave zwitterion (gas) -57.83940 function. From this data you can reason that the glycine 3. On the Properties tab, choose Hyperfine Coupling zwitterion is the more favored conformation in Constants. water and the neutral form is more favored in gas 4. Click Run. phase. The unpaired electron in the ethyl radical is delo- Example 6: Hyperfine Coupling Constants calized. Otherwise, there would be no coupling constants. This example uses the ethyl radical. To build the model: Hyperfine Coupling Constants 1. Go to File>New Model. 2. Click the Text Building tool. C1 0.02376 3. Click in the model window. A text box appears. C2 -0.00504 4. Type EtH and press the Enter key.

Chem & Bio 3D 145 User Guide z . Closed Shell Shell Closed and Spin Density PM3 Interface>Minimize Interface>Minimize hyl radical is more local- radical is hyl . orbital on C1. Generally, this is a good orbital on C1. Generally, Calculations>MOPAC Calculations>MOPAC You can look in the *.out file for a breakdown can look in the *.out file for of You z . Energy (Restricted) Density” on page 140. Total Spin Density Total 0.907440.00644 C1 C2 Atomic Orbital Spin Density Orbital Atomic -0.03463 A.O. -0.078960.078150.010460.054880.05329 p C2 H3 s H4 s H5 s H6 s H7 s 4. choose On the Propertiestab, indication of the reactive site indication of the reactive Example 8: RHF Spin Density this time radical, Thisethyl the example also uses density: spin to calculate the RHF 1.“Spin in described radical as ethyl Create the 2. Go to NOTE: the spin densities for each atomic orbital. 3. choose On the Theorytab, You can reason from the result shown that the result the shown from can reason You unpaired in the et electron ized at p The the total spin Messagedensi- displays window atom (spin densities for all orbitals ties for each are atom). each totaled for x y z x y orbitals). z and p y . Open Shell (Unre- , p x PM3 . in Density A.O. Spin Density and Calculations>MOPAC Interface>Minimize Interface>Minimize Calculations>MOPAC . 146 Chapter 10 Energy stricted) Density” on page 140. H3H4H5 -0.02632 H6 -0.02605 H7 0.00350 0.05672 0.05479 -0.01844 C2 p 0.083750.94768-0.01511-0.06345 C1 p C1 p C2 S C2 p Atomic Orbital Sp 0.071270.06739 C1 s C1 p Hyperfine Coupling Constants Example 7: UHF Spin Density Example 7: UHF calculate the UHF radical, Again, using the ethyl spin density: 1. in “Spin as described radical Create the ethyl 2. Go to 4. select On the Properties tab, 3. On the Theory select tab, The Message window displays a list of atomic a list of The displays Message window orbital spin densities. The value, atomic orbitalseach for are not labeled the generalruletable in the shown is however, p onlys, uses (MOPAC below

Administrator log box.The following information is found in the Total Spin Density summary file for each run:

0.00000 H3 • Electronic Energy (Eelectronic) • Core-Core Repulsion Energy (E ) 0.00000 H4 nuclear • Symmetry 0.00001 H5 • Ionization Potential 0.04395 H6 • HOMO/LUMO energies 0.04216 H7 The *.out file contains the following information by default. You can reason from this result that the unpaired electron in the ethyl radical is more localized on • Starting atomic coordinates C1. Generally, this is a good indication of the reac- • Starting Z-matrix tive site. • Molecular orbital energies (eigenvalues) MOPAC Files • Ending atomic coordinates The workings of many of the calculations can also CS MOPAC can use standard MOPAC text files be printed in the *.out file by specifying the appro- for input, and creates standard MOPAC output priate keywords before running the calculation. For files. These are especially useful when running example, specifying MECI as an additional key- repeat computations. word will show the derivation of microstates used Using the *.out file in an RHF 1/2 electron approximation calculation. For more information see “Using Keywords” on In addition to the Messages window, MOPAC cre- page 240. ates two text files that contain information about the computations. NOTE: Close the *.out file while performing MOPAC Each computation performed using MOPAC cre- computations or the MOPAC application stops functioning. ates a *.out file containing all information concern- ing the computation. A summary *.arax file is also created, (where x increments from a to z after each Creating an Input File run). The *.out file is overwritten for each run, but a new summary *.arax, file is created after each A MOPAC input file (.MOP) is associated with a computation (*.araa, *.arab, and so on.) model and its dialog box settings. The OUT and AAX files are saved by default to To create a MOPAC input file: the \MOPAC Interface subfolder in your My Docu- 1. Go to Calculations>MOPAC Interface>Create Input ments folder. You may specify a different location File. from the General tab of the MOPAC Interface dia-

Chem & Bio 3D 147 User Guide Run and click and choose a and choose will not be cor- examination messages for these appear at use the SADDLE keyword, keyword, the SADDLE at use . . The Open dialog box appears. . The Open dialog box . If you are opening a MOPAC file a model where areIf you MOPAC opening a multiple input files that containing MOPAC Calculations>MOPAC Interface Calculations>MOPAC Calculations>MOPAC Interface Calculations>MOPAC Run Save As MOPAC Job MOPAC calculation. click sponding to the type of job saved within the file spondingtosaved the type of job appears. To run a MOPAC job from a JDF file: job from a JDF run a MOPAC To 3. Go to 2.are specified, for the calculation After all settings Running MOPAC Jobs MOPAC Running to select a previously created Chem3D enables you job description file(JDF). The JDF file MOPAC can be thoughtto of as a set of Settings that apply a particular dialog box. create a JDF file: To 1. Go to Jobs Repeating MOPAC can calculation, you perform After you a MOPAC repeat the job as follows: All propertiesAll jobthe for requested in the appear iteration Only file. *.out jobs. NOTE: matically Rectify in the Building control panel. NOTE: model reactionor coordinate geometries. 4.run.to Select the JDF file corre-The dialog box 5. Click has an open valence, such as a radical, you can avoid can such as a radical, you having valence, has an open coordinates readjustedthe turning by by Chem3D offAuto- under instances of the Z-matrix input MOPAC of type This rectly displayed in Chem3D. files includes calculations th . Run Run Create dialog box dialog box and click and click OPAC Interface OPAC Run MOPAC Input File Input Run MOPAC . . The Calculations>M Run 148 Chapter 10 Input File Input to the filelocation. “Specifying the mation about the options see Electronic Configuration” on page 241. appears. A new model window appears displaying the initial appears displaying A new model window runs job results the and model. The MOPAC appear. 2. Type the full path of the MOPAC file or Browse Browse or file 2. MOPAC the of path full the Type 3. more infor- For Select the appropriate options. 4. Click Figure 10.13: The Run MOPAC Input File dialog File box Input The Run 10.13: MOPAC Figure 2. and click settings appropriate the Select Files Running Input to run you created previously Chem3D allows files. input MOPAC run an input file: To 1. Go to Figure 10.12: Creating an an file input Creating 10.12: Figure

Administrator 1. Go to Calculations>MOPAC Interface and choose You can create a structure from the ARC file as Repeat [name of computation]. The appropriate dia- follows: log box appears. 1. Open the ARC file in a text editor. 2. Change parameters if desired and click Run. The 2. Delete the text above the keywords section of calculation proceeds. the file as shown in the following illustration. Creating Structures From ARC Files 3. Save the file with a MOP extension. 4. Open the MOP file. When you perform a MOPAC calculation, the results are stored in an ARC file in the \MOPAC Interface subfolder in your My Documents folder.

Chem & Bio 3D 149 User Guide 150 Chapter 10

Administrator Chapter 11: Jaguar

Overview box appears, with Minimize as the default Job Type. SCHRÖDINGER® Jaguar is a high-performance 2. Use the defaults on the Jobs tab, or set your own ab initio package for both gas and solution phase parameters. simulations, with particular strength in treating metal containing systems. It is a practical quantum mechanical tool for solving real-world problems. Option Function Job Type Sets defaults for different NOTE: Jaguar must be purchased as a separate plug- types of computations. in.and is available only for ChemBio3D Ultra 11.0. Method Selects a method.

Chem & Bio 3D 11.0 offers the features listed Basis Set Specifies the basis set. Most below. The model window transparently provides methods require a basis set the data for creating Jaguar input files or running be specified. See the Jaguar Jaguar computations. Help file for exceptions. • Minimizing Energy/Geometry Wave Function Selects closed or open shell. • Optimize to Transition State See “Specifying the Elec- tronic Configuration” on • Predict IR and Raman Spectra page 241 for more details. • Computing Properties • Advanced Mode Polarization Specifies a polarization function for heavy atoms Academic customers may purchase Jaguar from (P, S, or heavier). CambridgeSoft, see http://www.chem3d.com for details. Commercial customers should go to Diffuse Adds a diffuse function to http://www.schrodinger.com for information. For the basis set. If you use a information on how to use Jaguar, see the docu- diffuse function, you mentation supplied with the Jaguar application. should also specify Tight Convergence on the Minimizing Energy Advanced tab. See the Jaguar manual for details. Minimizing energy is likely the first molecular computation you will perform on a model. You may Move Which Used for partial minimiza- minimize all or part of a model. If you are minimiz- tion. You may optimize the ing part of a model, make your selection of what to selected or unselected por- include or exclude before continuing. tion of the model, which- ever is more convenient 1. Go to Calculations>Jaguar Interface>Minimize (Energy/Geometry). The Jaguar Interface dialog

Chem & Bio 3D 151 User Guide . The link under the text text link under the terface >Predict terface IR on the Jaguar Inter-on the Jaguar Compute Properties Compute tab, select the propertiesselect the you tab, tab, type any additional keywords type any additional keywords tab, button. button. Thespectrum predicted Run Run . . Properties General Use Advanced Mode Online Jaguar Online Keywords Calculations>Jaguar In Calculations>Jaguar> Run Spectrum Jaguar Interface dialog box appears, with the appears, Interface dialog box Jaguar Properties tab selected. wish to calculate from the final optimized con- optimized the final from to calculate wish formation. to use to modify the want optimization. that you appears in the Spectrum Viewer. uar minimization routine on the model, the on the model, uar minimization routine MM2tooltoolbar on the Calculation is faster and usually adequate. 2. Select the properties to estimate. 3. the Click 4. the On 5. Click 3. the Click face submenu. face submenu. Note the the link opens clicking help, need If you window. pagethe of keywords to the browser web your site. Web Schrödinger Computing Properties to pre- the parameters for computations specify To dictproperties of a model: 1. Go to Advanced Mode gocan you directly to a are an expertIf you user, text entry similar to the input template. window click Just Predicting Spectra Predicting predict an IR spectrum: To 1. not run have the Jag- minimization. a you If Run 2. Go to 3. On the

Use Formal Charge Coordinate radio button. is not reached minimum Default is 100. sooner. is 1. deselect- charge negative by ing the checkbox and entering a checkbox value. . The Jaguar Interface dialog box Interface dialog box . The Jaguar Calculations>Jaguar Interface>Optimize to Interface>Optimize Calculations>Jaguar Unless you are an experienced Jaguar user, use the user, areUnless you an experienced Jaguar 152 Chapter 11 appears. appears. parameters. Transition State Transition Coord. System Select Cartesian or Internal Max Iterations if iterations, Maximum PressureTemperatureSpin Multiplicityatm. Default is 1 Default (298.15°K). is 0°C Default integer. positive A Net Charge or a set positive may You Option Function 2. own your or set defaults, use the may You NOTE: State defaults. Transition Optimize to Transition State Optimize to Transition model to a use a transition your optimize state, To conformationtransitionstate asto the close that is Do not use a local or global minimum, as possible. the because the algorithm move cannot effectively geometry from that starting point. optimize a transition state: To 1. Go to

Administrator Chapter 12 : GAMESS Computations

GAMESS Overview run any computation using any of the options as a starting point. If you are familiar with the The General Atomic and Molecular Electronic GAMESS keywords, you can choose Use Advanced Structure System (GAMESS) is a general ab initio Mode and get a GUI version of the command line quantum chemistry package maintained by the interface. Gordon research group at Iowa State University. It computes wavefunctions using RHF, ROHF, UHF, Minimizing Energy GVB, and MCSCF. CI and MP2 energy corrections are available for some of these. To perform a GAMESS Minimize Energy computation on a model: GAMESS is a command-line application, which requires a user to type text-based commands and 1. Go to Calculations>GAMESS>Minimize Energy. data. Chem & Bio 3D 11.0 serves as a front-end The Minimize Energy dialog box appears with graphical user interface (GUI), allowing you create the Job & Theory tab displayed. and run GAMESS jobs from within the applica- 2. Use the tabs to customize your computation. See tion. the following sections for details. The GAMESS application is installed automatically 3. Click Run. with Chem & Bio 3D 11.0. You must, however, accept a license agreement and register the soft- The Job & Theory Tab ware before you can use it. Chem & Bio 3D 11.0 Use the Job & Theory tab to specify the combi- does this automatically the first time you use the nation of basis set and particular electronic struc- GAMESS computation option. The computation ture theory. By default, this tab is optimized for options on the GAMESS interface menu are: setting up ab initio computations. • Minimize Energy For more detailed information, see the $BASIS • Optimize to Transition State section of the GAMESS documentation. • Compute Properties To specify the calculation settings: •Run Frequency 1. From the Method list, choose a method. • Predict IR/Raman Spectra 2. From the Wave Function list, choose a function. • Predict NMR Spectra 3. From the Basis Set list, choose the basis set. When you choose one of these options, The GAMESS interface dialog box appears, with the NOTE: To use a Method or Basis Set that is not on the recommended default parameters for that compu- list, type it in the Additional Keywords section on the Gen- tation chosen. You may change parameters on any eral tab. For more information, see “Specifying the General of the tabbed pages of the dialog box before run- Settings” on page 154. ning the computation. Thus, the options are a convenience in that they insert defaults. If you know what parameter settings you want to use, you can 4. From the Diffuse list, select the diffuse function to add to the basis set.

Chem & Bio 3D 153 User Guide . Proper- General tab, set the following options: set the following tab, tab to customize the calculation to Properties General . • Select the properties to calculate •type Analysis Select the Population ties 2. On the the General Settings Specifying Use the tab The General 12.2: Figure Figure 12.1: The Properties tab Properties The 12.1: Figure 1. In the EnergyMinimize click dialog box, the model. settings: set the General To 1. In the Minimize Energy dialog box, click Job Job type Population Analysis Population value between 1 and 10. between value

Use Tight Convergence Cri- Convergence Use Tight teria Copy Measurements to Output Display Every Iteration Display recording or (Displaying iteration adds sig- each time the to nificantly required to minimize the structure.) Record Every Iteration functions. If you select a func- select a you If functions. Atom, also select an H option. also select Atom, tab properties to specify which

tab to set options for display and set options tab todisplay for

Spin Multiplicity Polarization Properties General tab. 154 Chapter 12 tion for Heavy tion for Type Opt=Tight calculate using the to the equivalent keyword Gamess view the value of view the value in measurement each the Measurement table watch the minimiza- watch at live tion process iteration in the each calculation If you want to … to you want If … click Then record each iteration record each as a frame in a movie for later replay is Mulliken. specify properties: To 6. a Select are computed. Theare computed. default Specifying Properties to Compute Specifying Properties the Use The General Tab The General the Use 5. the Set recording results of calculations. recording set the job type options: To 1. Energy In the Minimize the click box, dialog 2. Select the appropriate options:

Administrator 2. On the General tab, set the following options: 4. Select the .jdf or .jdt file type. • Select the Solvation model. 5. Click Save. • Type the dielectric constant for the solvent. Your custom job description appears in the The box does not appear for gas-phase com- GAMESS menu. putations. Running a GAMESS Job •In the Results In box, type or browse to the path to the directory where results are If you have a previously created an INP stored. GAMESS job file, you can run the file in Chem3D. • If desired, add GAMESS keywords to the To run the job file: Additional Keywords dialog box. 1. Go to Calculations >GAMESS>Run a Job. The Saving Customized Job Open dialog box appears. 2. Type the full path of the GAMESS file or Descriptions Browse to location. After you customize a job description, you can save 3. Click Open. The appropriate dialog box appears. it as a Job Description file to use for future calcula- 4. Change settings on the tabs if desired. tions. 5. Click Run For more information, see “Job Description File Repeating a GAMESS Job Formats” on page 128. To save a GAMESS job: After a GAMESS computation has been performed, you can repeat it using the GAMESS 1. On the General tab, type the name of the file in menu. the Menu Item Name text box. The name you To repeat a GAMESS job: choose will appear in the GAMESS menu. 2. Click Save As. The Save dialog box appears. 1. Go to the Calculations>GAMESS>Repeat [name of 3. Open the folder: computation]. The appropriate dialog box appears. \Chem3D\C3D Extensions\GAMESS Job. 2. Change parameters if desired and click Run.

NOTE: You must save the file in the GAMESS Job folder for it to appear in the menu.

Chem & Bio 3D 155 User Guide 156 Chapter 12

Administrator Appendix A: Substructures

A substructure is defined as part of a molecular to position the substructure relative to other atoms structure that has attachment points to which other when the substructure is used to convert labels atoms or substructures connect. into atoms and bonds. You can define substructures and add them to a For example, Chem & Bio 3D 11.0 stores with the substructures table. When you define a substruc- substructure a dihedral angle formed by two atoms ture, the attachment points (where the substructure in the substructure and two unselected atoms. If attaches to the rest of the structure) are stored with more than one dihedral angle can be composed the substructure. from selected (substructure) and unselected If a substructure (such as Ala) contains more than (non-substructure) atoms, the dihedral angle that is one attachment point, the atom with the lowest saved with the substructure consists of the atoms serial number normally becomes the first attach- with the lowest serial numbers. ment point. The atom with the second lowest serial Consider the following model to define a substruc- number becomes the second attachment point, and ture for alanine: so on. Attachment point rules The following rules cover all possible situations for multiple attachment points in substructures; Rule 3 is the normal situation described above: • If two atoms are the same according to the above criteria, the atom with the lowest serial number goes first. • If an atom has an open valence and is attached to a selected atom, it is numbered after any Since polypeptides are specified beginning with the atom that is attached to an unselected atom. N-terminal amino acid, N(4) should have a lower • If an atom is attached only to rectified atoms, it serial number than the carboxyl C(6). To ensure goes after any atom that is attached to non-rec- that a chain of alanine substructures is formed cor- tification atoms. rectly, C(1) should have a lower serial number than • If two atoms are the same according to the O(3) so that the C-C-N-C dihedral angle is used to above criteria, then the one attached to the position adjacent substructures within a label. atom with the lowest serial number goes first. Defining Substructures Angles and measurements To define a substructure: In addition to the attachment points, the measurements between the selected atoms and nearby 1. Build a model of the substructure. You can use unselected atoms are saved with the substructure Chem & Bio 3D 11.0 tools or build it in the ChemDraw panel.

Chem & Bio 3D 157 User Guide ester onto the end of the end the onto ester When defining substructuresmultiple attach- with NOTE: section. : atom in the ester has Notice that the carbon when the Thisreplaced is because, the hydrogen. atomhad defined, the carbon a lower ester was atom that (3) than the oxygen serial number formed in the substruc-point the other attachment ture (5). ment points, it is critical to note the serial numbers of the numbers of serial note the to critical is it ment points, substructure can correctly the atoms in you so that the orient substructure it is inserted in the model. See the ruleswhen for this of points discussed at the beginning attachment multiple If you want to append an append to want you If a hydrogen double-click acid, as a carboxylic chain to replaceas the name of ester (as long itwith the H(8) the substructure Replacing textbox). in the is fol- the structure)(of the original produce would lowing: . from the from

Paste column. column. Name Model . . A new row is added to the table. is added to the . A new row consider an ester substructure,

. You can build this substructure can as part . You 2 View>Parameter Tables>Substructures View>Parameter Edit>Copy COOR 158 context menu. Note that the content will be not be that the content will Note contextmenu. tocell. another move be visible until you Append Row 1 6. the cell in the Select 3. in the Substructures Right-click table and choose 4. the cell in the Select Select atoms 3-5 (the two oxygens and the oxygens carbon Select atoms 3-5 (the two and using the instructionsthem) between above, Substructures in the record create a new Table. : To save the substructure save definition: To 1. Open Substructures.xml. 2.to Go 2.define. atoms to the Select 3. Go to of the following model: of the following 7. substructure. the for a name Type 8. the Substructures Close and save table. For example, R 5. in the cell and choose Right-click

Administrator Appendix B: keyboard modifiers

The following tables list the keyboard modifiers that allow you to manipulate your view of the model without changing tools. Rotation

Key Drag Shift+Drag

ALT Trackball rotate view Trackball rotate model selection V Rotate view about selected bond Rotate model selection about axis X Rotate view about view X axis Rotate model about view X axis Y Rotate view about view Y axis Rotate model about view Y axis Z Rotate view about view Z axis Rotate model about view Z axis Shift+B Rotate 1/2 of fragment around bond Shift+N which fragment rotates depends on the order in which the atoms were selected.

Key Drag Shift+Drag

ALT Trackball rotate all objects Trackball rotate the selected object(s). At least one object must be selected. Shift+B Rotate 1/2 of fragment around bond Shift+N which fragment rotates depends on the order in which the atoms were selected. V Rotate all objects (one bond must Rotate model about the axis. The model be selected) that includes the selected bond rotates around the bond. X Rotate all objects about X axis Rotate model about the X axis Y Rotate all objects about Y axis Rotate model about the Y axis Z Rotate all objects about Z axis Rotate model about the Z axis

Chem & Bio 3D 159 User Guide moves moves Multiple box select Multiple box atoms /bonds Shift+Drag e mouse while holding down down holding while e mouse the Model Explorerdis- Model or 3D the Tip: The order is important;The order Tip: pressthe to it. Double-clicking an atom or bondselects the fragment to it. Double-clicking /bonds Drag selects the next higher fragment; that is, each double-click selects the next each double-click higher fragment; that is, ll wheel to zoom. Draggingor with the middle button a model dragging by with th Shift+Drag ng the shift key down while making the selections down ng the shift key submenu of the context menu in of the context menu submenu Select Shift+Click Drag Move all objectsall Move Zoom to center Zoom to rotation center center Zoom to selection model the selected Move Select atom/bondatom/bondselect Multiple atoms select Box Click 160 Key S CTRL A Q W Key play. play. holdi selections by multiple specify In all cases, . that atom or bond belongs to. Double-clicking a selected fragment Double-clicking that atom or bond belongs to. Radial Selection Radial selectionselection of an object is or groupbased of objects on the distance orselected radius from a Thisgroupobject or feature is particularly ofhighlighting objects. useful for the binding site of a protein. Radial selection is accessed through the NOTE:and the two a bond selectsthe bond atoms connected Clicking haveuntilentire selected the you up one in the hierarchy you model. If you have a wheel mouse, you may also use the scro also may you mouse, a wheel have If you Selection Selection Standard scroll wheel translates the view. scroll wheel translates Zoom and Translate Zoom and In addition to the keyboard shortcuts, you can rotate can you In addition shortcuts, to the keyboard button. mouse the left wheel and scrollbutton or mouse middle theboth middle button first.

Administrator Select Atoms within Distance of Selection. Selects all atoms (except for those already selected) lying within the specified distance from any part of the current selection. The current selection will be un-selected unless multiple selection is used. Select Groups within Distance of Selection. Selects all groups (except for those already selected) that contain one or more atoms lying within the specified distance from any part of the current selection. The current selection will be un-selected unless multiple selection is used. Select Atoms within Radius of Selection Centroid. Selects all atoms (except for those already selected) lying within the specified distance of the centroid of the current selection. The current selection will be unselected unless multiple selection is used. Select Groups within Radius of Selection Centroid. Selects all groups (except for those already selected) that contain one or more atoms lying within the specified distance of the centroid of the current selection. The current selection will be un-selected unless multiple selection is used.

Chem & Bio 3D 161 User Guide 162

Administrator Appendix C: Building Types

Building types define the structure of your model– • The number of double, triple and delocalized the bond lengths, bond angles, and relative sizes of bonds. the atoms themselves. By default, Chem & Bio 3D assigns building types as you build your model. Chem & Bio 3D includes a predefined set of build- NOTE: For comparing bond orders, a building type that ing types. However, you can also create your own. contains one double bond may be assigned to an atom that contains two delocalized bonds, such as in benzene. Assigning building Types When you replace atoms, Chem & Bio 3D If the maximum ring size field of a building type is attempts to assign the best type to each atom by specified, then the atom must be in a ring of that comparing the information about the atom (such size or smaller to be assigned the corresponding as its symbol and the number of bonds) to each building type. record in the Atom Type table. If an atom is bound to fewer ligands than are spec- When you have selected the Correct Building Type ified by a building type geometry but the rectifica- check box in the Model Building tab (File>Model tion type is specified, then the atom can be Settings>Model Building tab), building types are cor- assigned to that building type. Open valences are rected when you delete or add atoms or bonds. In filled with rectification atoms. addition, the building types of pre-existing atoms For example, consider the building types for the may change when you replace other atoms with following structure of ethanoic acid: other atoms of a different type. Building Type Characteristics The characteristics of an atom must match the following type characteristics for Chem & Bio 3D to assign the type to the atom. • The symbol. • The bound-to type (if specified for the building type). • The bound-to order (if the bound-to type is specified). O(3) matches the criteria specified for the building type O Carbonyl. Specifically, it is labeled ‘O’, it is bound to a C carbonyl by a double bond; it is attached to exactly one double bond and no triple bonds.

Chem & Bio 3D 163 User Guide The Chem3D Building Atom Types The Building Chem3D Atom Types View>Parameter Tables>Chem3D Building Tables>Chem3D View>Parameter Atom Types. Atom Types. table opens in a window. to changeand new information. type want parameter is for the thatthe name Be sure table. in the table. duplicated elsewhere not newly defined building type. Defining building types Defining whether to types, need to define building If you types table for building or to add to the building add to a file format interpreter for importing, here is the procedure: 1. Go to 2. you cell that the in click edit a building type, To 3.of the field the appropriate data in each Enter 4. can use the now You the table. Save and Close same as same the rectification 1 typein (number pri- the other the over precedence is given list above) ority type is building the O Carboxyl possibilities, two atom. the oxygen assigned to assigned to atoms in the to atoms assigned 164 fied and are not the same as their rectification as their rectification same the not fied and are types. types. their rectification as fied and are the same specified. following order:following 1.speci-are types whose bound-to Building types 2.speci-are types whose bound-to Building types 3.notare whose bound-to types Building types O(4) depicted in the model above, example, For First, it types. building could be one of several the bound-to for which an O Ether atom could be 3, above). (priority number type is unspecified Alcoholfor which it could be an O Alternatively, the rectificationsame as the the bound-to type is third A H Alcohol 2, above). (prioritytype, number the bound-to for which Carboxyl, possibilityis O CarbonylCthe rectification type is H and type is 1). Because the charac- number (priority Carboxyl bound-to type that is not the a specified teristic of If an atom can be assignedatom can If an one more than to build- building types are ing type,

Administrator Appendix D: 2D to 3D Conversion

This section describes how Chem & Bio 3D 11.0 where the atom at the wide end of the bond is in performs the conversion from two to three dimen- front of the atom at the narrow end of the bond. sions. You can open a 2D drawing using several Wedged hashed bonds indicate the opposite: the methods. atom at the wide end of a wedged hashed bond is behind the atom at the other end of the bond. • Opening a Chem & Bio Draw or ISIS/Draw document. • Pasting a Chem & Bio Draw or ISIS/Draw structure from the Clipboard. • Opening a Chem & Bio Draw connection table file. While Chem & Bio 3D can read and assimilate any As shown above, the two phenyl rings are a trans Chem & Bio Draw structure, you can assist Chem formation about the cyclopentane ring. The phenyl & Bio 3D in the two- to three-dimensional conver- ring on the left is attached by a wedged hashed sion of your models by following the suggestions bond; the phenyl ring on the right is attached by a in this Appendix. wedged bond. Chem & Bio 3D uses the atom labels and bonds You can also use dashed, hashed, and bold bonds. drawn in ChemDraw to form the structure of your However, you should be aware of potential ambi- model. For every bond drawn in ChemDraw, a cor- guity where these non-directional bonds are used. responding bond is created in Chem & Bio 3D. A dashed, hashed, or bold bond must be between Every atom label is converted into at least one one atom that has at least three attachments and atom. one atom that has no more than two attachments, Dative bonds (see figure below) are converted to including the dashed, hashed, or bold bond. single bonds with a positive formal charge added Shown below, the nitrogen atom is placed behind to one atom (the atom at the tail of the dative the ring system and the two methyl groups are bond) and a negative formal charge added to the placed in front of the ring system. Each of these other (the head of the dative bond). three atoms is bonded to only one other atom, so they are presumed to be at the wide ends of the stereo bonds.

Stereochemical Relationships Chem & Bio 3D 11.0 uses the stereo bonds H-Dot, and H-Dash atom labels in a Chem & Bio Draw structure to define the stereochemical relationships in the corresponding model. Wedged However, in the next figure (below), the hashed bonds in Chem & Bio Draw 11.0 indicate a bond bond is ambiguous because both atoms on the hashed bond are attached to more than two bonds.

Chem & Bio 3D 165 User Guide to determine the atom types

As a generalAs a rule, you stereo bonds the more model, the include greater in your is the probability correct will make Bio 3D 11.0 & that Chem dihedral angles. and chirality for choices structures, two-dimensional When converting bond lengths 3D 11.0 uses standard Chem & Bio and angles in the currentspecified as set of param- 11.0 tries to translate Chem & Bio 3D If eters. will not be closures the ring systems, strained ring of the correct length angle. or Labels Chem & the atom Bio 3D 11.0 uses labels in a two- dimensional structure be Unlabeled to atoms are assumed atoms. the of into atoms and bonds carbon. Labels are converted the to convert method as that used using the same Therefore, and bonds. into atoms text in a textbox substruc-even or atoms labels can contain several tures. can specify a cis fusion a cis specify can 166 Appendix D . H-Dots and H-Dashes are also used to indicate also used to indicate are and H-Dashes H-Dots atoms H-Dots become hydrogen stereochemistry. wedgedbond. a to carbon atoms by attached a by atoms attached hydrogen become H-Dashes bond. wedged hashed the left on cis-decalin figure shows The following be right as they would the on trans-decalin and Chem by be read in to Bio Draw & Chem in drawn you Of course, & Bio 3D. with two H-Dots instead of two H-Dashes H-Dots instead of two with two In this case the hashed bond is treated like a solid solid a like is treated bond hashed the case In this solid like treated bonds always are Wavy bond. bonds.

Administrator Appendix E : File Formats

Editing File Format Atom Types by the file format. All names must be unique. The records in the table window are sorted by name. Some file formats contain information that describes the atom types. Typically, these atom types are ordered by some set of numbers, similar NOTE: While names are similar to atom type numbers, to the atom type numbers used in the Atom Types they do not have to correspond to the atom type numbers of table. If the file format needs to support additional atom types. In some cases, however, they do correspond. types of atoms, you can supply those types by editing the file format atom types. Chem & Bio 3D 11.0 uses XML tables to store file Description formats. You can edit these tables in any text editor The second field contains a description of the or in Chem & Bio 3D. Go to View>Parameter Tables) atom type, such as C Alkane. This description is and select the table you want to edit. included for your reference only. The remaining fields contain information corre- TIP: The XML files are in the path ...\Chem3D\C3D sponding to the information in an Atom Types Items\ table. File Format Examples Name The following sections provide examples of the Each atom type is described by a name. This name files created when you save Chem3D files using the is a number found in files of the format described provided file formats. Alchemy File The following is a sample Alchemy file (Alchemy) created using Chem3D for a model of cyclohex-

Chem & Bio 3D 167 User Guide Atom types in the Alchemythe Atom types in file format are user- Alchemy III is a registeredAlchemy is a III trademark of Tripos informationbondsthe in the of about each Thefield is the bond number first molecule. bonds), of the (rangingfrom 1 to the number atom the of is the serial number field second third field is the the where the bond begins, of the atom where serial the bond number and the fourth The field is the bond type. ends, total number of atoms in the molecule and the the molecule in of atoms total number of bonds. number is the total field second The of about in the molecule. the atom each first field of the is the serial number atom. The the third field is is the atom type, field second fourththe the is field the X coordinate, Y coordinate and the fifth field is the Zcoordinate. 3334 1335 1436 15 437 16 538 17 540 18 14 5 19 6 6 15 6 SINGLE 16 7 SINGLE 17 SINGLE 18 SINGLE 19 SINGLE SINGLE SINGLE •describing contain 4 fields 21–40 each Lines •The is the first field fields. Line 1 contains two • contain 5 Lines fields of information2–20 each NOTE: 167 for instructions on modifying or creating type. an atom NOTE: Inc. Associates, line representsEach a datarecord containing one fields of informationor more molecule. about the below: described are Chem3D The by used fields Figure E.3Alchemy file format E.3Alchemy Figure definable. See “Editing File Format Atom Types” on page Atom Types” See “Editing File Format definable. 19 19 BONDS ATOMS 2 1 C3C3 1 2 -1.12363 2 -0.26 -0.1774 0.059 5 -0.856 3 C36 -1.0224 4 C37 1.01 5 C38 1.838 6 C39 0.9934 -0.0491 7 O310 0.1626 -1.3267 -0.2815 8 H 0.854311 -0.0526 9 H -2.1621 0.0527 1.0252 12 10 H -1.0585 1.3275 -1.444813 H 11 0.3907 -0.8497 0.818514 0.0275 12 H -0.979 -0.3338 15 1.6239 13 H -1.8784 -1.9623 16 0.729 14 H -0.6806 -0.579417 2.197 15 H -2.0941 0.940818 2.7422 16 H -0.8229 -1.7589 19 1.5961 17 H 0.7763 0.3289 20 0.7156 18 H 0.9769 -0.282 21 -0.8718 19 H 1.8784 1.9574 22 -0.004 0.6068 1 0.679 23 -2.7422 2 2.0941 -0.931924 -0.593 3 1.7721 125 4 0.9688 126 5 127 6 2 128 7 6 229 8 7 230 9 SINGLE 8 231 10 SINGLE 3 332 11 SINGLE 9 3 12 SINGLE 3 10 SINGLE 4 4 SINGLE 4 11 SINGLE 12 SINGLE 5 SINGLE 13 SINGLE SINGLE SINGLE 119 119 Figure E.3Alchemy E.3Alchemy format file Figure anol. Theanol. first in the column are line numbers only. for reference are added that numbers 168

Administrator possible bond types are: SINGLE, DOUBLE, In Cart Coords 2, the atom type number for all TRIPLE, AMIDE, or AROMATIC. Note that atom types is computed by multiplying the atomic all the bond order names are padded on the number of the element by 10 and adding the num- right with spaces to eight characters. ber of valences as specified by the geometry of the atom type. These numbers are also generally fol- FORTRAN lowed by the program MacroModel. The FORTRAN format for each record of the For example, the atom type number for C Alkane Alchemy file is as follows: (a tetrahedral carbon atom) is 64 using Cart Coords 2. Line Description FORTRAN To examine the atom types described by a file for- Number Format mat, see “Editing File Format Atom Types” on page 167. 1 number of atoms, I5, 1X, number of bonds ATOMS,1X,I5, The Cartesian Coordinate File Format 1X, BONDS The format for Cartesian coordinate files may be 2–20 atom serial num- I6,A4,3(F9.4) described as follows: ber, type, and 1. The first line of data contains the number of coordinates atoms in the model. 21–40 bond id, from I6,I5,I6,2X,A8 Optionally, you can follow the number of atoms in atom, to atom, the file with crystal cell parameters for the crystal bond type structure: a, b, c, α, β, and γ. Following the cell parameters, you can also include an exponent. If Cartesian Coordinate Files you include an exponent, then all of the fractional cell coordinates will be divided by 10 raised to the Two file formats are supplied with Chem & Bio power of the exponent. 3D that interpret Cartesian coordinate files. These 2. The first line of a Cartesian coordinate file is fol- formats, Cart Coords, Cart Coords 2, interpret text lowed by one line of data for each atom in the files that specify models in terms of the X, Y, and model. Each line describing an atom begins with Z coordinates of the atoms. These file formats can the symbol for the atom. This symbol corre- also interpret fractional cell coordinates in orthog- sponds to a symbol in the Elements table. The onal or non-orthogonal coordinate systems. symbol can include a charge, such as N+. The Building Types symbol is followed by the serial number. Two file formats are supplied with Chem3D that 3. The serial number is followed by the three coor- interpret Cartesian coordinate files. The difference dinates of the atom. If you have specified crystal between the two file formats are the codes used to cell parameters in the first line of the file, then convert atom type numbers in the file into atom these numbers are the fractional cell coordinates. types used by Chem3D. Otherwise, the three numbers are X, Y, and Z Cartesian coordinates. In Cart Coords 1, atom types are numbered 4. Following the coordinates is the atom type num- according to the numbering used by N.L. Allinger ber of the atom type for this atom. This number in MM2. These numbers are also generally fol- corresponds to the code of an atom type record lowed by the program PC Model.

Chem & Bio 3D 169 User Guide 2 1 51 53 53 54 54 55 55 13 5 1819 56 57 57 - 0.43226 0.45701 6 1.46560 7 0.62580 - 1.62942 5 2 0.43771 4 0.64665 1.59346 6 1 10 - 0.61828 -1.627 5 6 - 1.52456 0.27125 5 1.48999 21 10 1.5595 25 2.1250 46 0.6405 18 0.2816 - 0.7623 14 -0.8781 1.47006 - 0.4102 3 - 2.2463 1 -1.1698 - 1.8096 31 - 0.7613 7 - 1.7316 1 - 1.6852 4 1.8656 31 97 1.21162 4 1.2089 69 2.5249 18 1.11557 27 58 48 0.8944 4 93 98 1.2950 59 1.2651 3 94 H 9 1.0525 H10- H11- H12- H13- H140.9370 H152.3297 H161.0034 C6 - O 101 1.1929 H171.0057 H18- H19- H 102 2.1275 Components of a CartesianComponents of coordinatefile with of for C(1) Number Serial by Connection Table Figure E.1. inCyclohexanol is shown 11 3 1011 12 6 1213 11 5 1415 14 6 1617 0.50882 1 2 40.50878 99 10 - 0.66891 0.50886 5 - 0.66444 1.0661 93 1.0755 77 0.2755 13 - 0.3863 2 - 1.1915 4 1.4090 1 85 28 9 0.8347 3 specified in the file format atom type table. For For file format in the specified table. type atom information,more File Format “Editing see on page167. Types” Atom can specify up to ten You for the atom. tion table The connectiontable for a Carte- atoms. other two listedbecan one of in file sian coordinate ways: by serial numberor byposition. can flowofdescriptions the the you atoms, corre- of lines atoms with an equal number same atoms with differentthetosponding coor- Chem3D generates independent views dinates. coordinates. usingsets of the additional C3 - C 4 1.2172 C 5 0.6393 19 C 1 0.7066 C2 - 5. connec- is the type number the atom Following use the serial number serial Connection tables by determine atom to each of number number the that appears in the connection table of other be therefore, must, numbers All serial atoms. unique. posi- position relative use the Connection tables by thein file to determine tions of the atoms the thein con- atom that appear will each for number The is atom first atoms. other of table nection is 2, etc. 1, the second number 6. views of multiple create the same set of To : 170

Administrator Figure E.1: Connection table by serial number Cartesian coordinate File (Connection Table by Serial Number or Position): Element X, Y and Z Serial Numbers of Other Atoms Symbol Coordinates to which C(1) is Bonded Line Description FORTRAN C 1 0.706696 1.066193 0.508820 1 2 4 9 101 Number Format

Serial Atom Type Number Text Number 1 Number of I3 Atoms 2 to end Atom coordi- A3, 1X, I4, 3(1X, Components of a Cartesian coordinate file with nates F11.6), 1X, I4, Crystal coordinate Parameters for C(1) are shown 10(1X, I4) Figure E.2. Cartesian coordinate File (Fractional Crystal Cell Figure E.2: Connection table by crystal co-ordinate parameters Parameters): Number of Atoms abc αβγ Exponent Line Description FORTRAN

43 10.23 12.56 8.12 90.0 120.0 90.0 4 Number Format

C 1 1578 -2341 5643 1 20 21 22 1 Number of I3, 6(1X, F), I Fractional Cell Atoms, Crystal Coordinates Cell Parameters Components of a Cartesian Coordinate file with 2 to End Atom coordi- A3, 1X, I4, 3(1X, Connection table by Position for Cyclohexanol is nates F11.6), 1X, I4, shown in Figure E.3. 10(1X,I4) Figure E.3: Connection table by position

Element X, Y and Z Positions of Other Atoms Cambridge Crystal Data Bank Files Symbol Coordinates to which C(1) is Bonded You can import Cambridge Crystal Data Bank

C 1 0.706696 1.066193 0.508820 1 2 47 8 (CCDB) files but not save files in the CCDB format. Chem & Bio 3D uses the FDAT format of Serial Atom Type CCDB, described on pages 26–42 of the data file Number Text Number specifications of the Cambridge Structural Data- base, Version 1 File Specifications from the Cam- FORTRAN Formats bridge Crystallographic Data Centre. For further The FORTRAN format for a Cartesian coordinate details about the FDAT format, refer to the above file with a connection table is described in the fol- publication or contact the Cambridge Crystallo- lowing tables: graphic Data Centre. As described in the specifications of the Cam- bridge Crystal Data Bank format, bonds are automatically added between pairs of atoms whose distance is less than that of the sum of the covalent radii of the two atoms. The bond orders are

Chem & Bio 3D 171 User Guide 0 172.653 2 3- 1 57.0318 0 3 -55.6959 0 9 5 2 2 109.39 4 109.39 -1 2 107.698 1 111.703 22 55.3112 110.753 0 1 111.7729 2 109.713 2 5 5 2 7 6 5 You cannot position an atom in terms atom in an position later- cannot of a You 511.1174 6 1 1.4019 1 3 1.5341 1 4 1.5359 1 1 1.5396 1 1 1 1.5414 1 2 1.5352 defining atom. All angles are measured in in are measured angles All atom. defining degrees. a second defining ond angle-defining atom and is a number Finally, the first angle. follows angle second angle. the type of the that indicates given angle the second zero, is angle type If the second – Distance-defin- dihedral angle: New Atom is a ing Atom – First Angle-defining Atom – Second Angle-definingOtherwise Atom. the third angle Atom – Distance-definingangle: bond New is a If the sec- Atom. Atom – Second Angle-defining ond angletype is then1, the new atom is defined relationship to the three using a Pro-R/Pro-S defining atoms; if the second angle type is -1, the relationship is Pro-S. NOTE: positioned atom. of an Internal is a sample The following coordi- in nates output file for cyclohexanol, created Chem3D: 5. of a sec- 5, the serial number Beginning with line Covalent Radii Each subsequent linesubsequent begins with the building Each type number. Origin atom. of the atom to the serial number by followed is and the distance bonded is the new atom which the first Theto that atom. always origin atom is All distances distance-defining atom in the file. are measured in Angstroms. angle-defining atom of the first the serial number the newly defined and the angle atom, between angle- and the first the distance-defining atom, TripleDouble 0.81 Delocalized 0.87 0.93 Single 1.00 Bond TypeBond of / Sum Distance Actual Internal Coordinates File Internal Coordinates Internal(INT Coords) are text coordinates files internal the files that describe a single molecule by atom. The coordinates used to position each serial determinedatoms are of the the order by numbers of 1, Thefirst atom has a serial number in the file. 2, etc. is number the second The format for Internalfiles is as fol- coordinates lows: 1. Chem3D. ignored by line comment Line 1 is a 2. Line 2 contains the building type of number the 3. Beginning with building type number line 3, the 4. by followed is Beginning with line 4, the distance guessed based on the ratio of the actual distance to distance of the actual ratio on the based guessed radii.The orders, bond covalent of the the sum and the atom symbols arebond used angles, to determine the in atoms the types of the atom model. 172

Administrator 521.11621 109.41 3 109.41 1 listed on one line. The serial number of the first 9 atom is 1, the second is 2, etc. In the prior Internal 521.11561 109.41 3 109.41 -1 coordinates output example of cyclohexanol, the 8 numbers 5 and 6 are on a line at the end of the file, 531.11662 109.41 6 109.41 -1 and therefore the ring closure is between the fifth 4 atom and the sixth atom. 531.11602 109.41 6 109.41 1 If a bond listed at the end of an Internal coordi- 6 nates format file already exists (because one of the 541.11541 109.41 5 109.41 1 atoms on the bond is used to position the other 2 atom on the bond) the bond is removed from the 541.11491 109.41 5 109.41 -1 model. This is useful if you want to describe multi- 3 ple fragments in an internal coordinates file. 551.11664 109.41 6 109.41 1 4 Atom Type Text Numbers Bond 551.11614 109.41 6 109.41 -1 Lengths 7 Origin Atom 1 First Angles 561.11663 109.41 5 109.41 1 4 Second Atom 1 1 1.54146 Second Angles 561.11603 109.41 5 109.41 -1 Third Atom 1 2 1.53525 1 111.7729 6 2 7 0.942 1 106.899 2 59.999 0 Fourth Atom 1 1 1.53967 2 109.7132 3 -55.6959 0 1 8 Distance-defining First Angle- Second Angle- Indicates Atoms defining Atoms defining Atoms Dihedral

56 Components of an Internal coordinates File for Bonds C(1) through C(4) of Cyclohexanol Bonds are indicated in Internal coordinates files in In this illustration, the origin atom is C(1). C(2) is two ways. connected to C(1), the origin and distance defining First, a bond is automatically created between each atom, by a bond of length 1.54146 Å. C(3) is con- atom (except the Origin atom) and its distance- nected to C(2) with a bond of length 1.53525 Å, defining atom. and at a bond angle of 111.7729 degrees with C(1), defined by C(3)-C(2)-C(1). C(4) is attached to C(1) Second, if there are any rings in the model, ring- with a bond of length 1.53967 Å, and at a bond closing bonds are listed at the end of the file. If angle of 109.7132 degrees with C(2), defined by there are ring-closing bonds in the model, a blank C(4)-C(1)-C(2). C(4) also forms a dihedral angle of line is included after the last atom definition. For -55.6959 degrees with C(3), defined by C(4)-C(1)- each ring-closure, the serial numbers of the two C(2)-C(3). atoms which comprise the ring-closing bond are

Chem & Bio 3D 173 User Guide 0 0 0 0 0 0 0 0 0 0 0 0 0 0.30 1.05 5 0.67 9 1.58 7 - 0.92 0.49 7 - 0.10 - 0.62 0.45 9 0.27 7 1.96 8 2.45 1 0.92 5 - 0.350 1 0.380 6 - 0.740 - 0.413 - 1.222 - 0.048 1.056 6 1.525 1 - 0.083 - 1.603 - 0.340 - 1.972 - 1.742 1.39 6 2 0.45 5 0 1 2 2 0.60 6 2.06 8 1.05 3 7 2 0.05 8 1 0000- 1 00000.51 1 00001.30 1 00000.37 1 0000- 8 1 3 5 7 MacroModel is MacroModel the Department within produced New York, Chemistryof at Columbia University, The file formatMacroModel the in defined is N.Y. Structure“MacroModel 2.0 docu- Files” version file that is a sample Thementation. following a model of cyclohexanol. describes 4 100 0 00 0 00001.97 4 100 0 00 0 00001.96 1 100 0 00 0 0000- 2 100 0 00 0 0000- 2 100 0 00 0 00000.12 3 100 0 00 0 00001.22 3 100 0 00 0 0000- 19 19 cyclohexan ol 32161711 4 1 3 1 131 8 19 1 0000- 4 1 321411011 331511211 341611411 311511611 4 1 4 1 4 1 4 1 4 1 F9.5 1X, F9.5) I3, I4, 3(1X, I4 1X, F9.5), 2(1X, I4) Format -55.698° Dihedral Angle 4 Chem3D 3 109.713° 111.771° 1.540 Å 2 1 1.535 Å CommentOrigin Atom Ignored by Second AtomThird Atom Atom to Fourth I4 Last Atom 1X, I4, 1X, I3, Blank Line Ring Closure I3, I4, 2(1X, Atoms Line Number Description FORTRAN 1.541 Å FORTRAN Formats FORTRAN formatsThe FORTRAN for the records in an Internalas follows: are coordinates file This portion of the Internal file for coordinates C(1) through C(4) of Cyclohexanol can be repre- structural the following diagram:sented by 174

Administrator 4 5 100 0 00 0 00000.98 1.921 - 0 Atom colors are ignored by Chem3D. This field 1 1 4 0.99 will contain a zero if the file was created using 4 6 100 0 00 0 0000- 2.283 0.03 0 Chem3D. 1 1.30 2 7 9 NOTE: Atom types are user-definable. See “Editing File 4 6 100 0 00 0 0000- 2.031 1.27 0 Format Atom Types” on page 167 for instructions on mod- 1 0.03 7 2 ifying or creating an atom type. 3 4 1 100 0 00 0 0000- 0.717 1.88 0 1 2.05 2 1 For example, the following illustrates the atom and 2 bond components for C6 and bond 3 of cyclohex- 4 1 100 0 00 0 00000.27 0.374 - 0 anol: 2 5 5 9 2.41

Each line represents a data record containing one Each pair of numbers represents an or more fields of information about the model. atom to which this atom is bonded Atom Color Each field is delimited by space(s) or a tab. 3 11 5 1 16 1 17 1 0 0 0 0 -0.606857 1.525177 0.459900 0 The fields in the MacroModel format file used by Atom Type Serial Number Bond Type X Y Z Chem3D are: Coordinates

1. Line 1 contains 2 fields: the first field is the num- FORTRAN Formats ber of atoms and the second field is the name of the molecule. The molecule name is the file The FORTRAN format for each record of the name when the file is created using Chem3D. MacroModel format is as follows: 2. Lines 2-19 each contain 17 fields describing information about one atom and its attached Line Description FORTRAN bond. The first field contains the atom type. The Number Format second through thirteenth fields represent 6 pairs of numbers describing the bonds that this 1 number of atoms and 1X,I5,2X,A atom makes to other atoms. The first number of molecule name (file each pair is the serial number of the other atom, name and the second number is the bond type. The fourteenth field is the X coordinate, the fifteenth MDL MolFile field is the Y coordinate, the sixteenth field is the The MDL MolFile format is defined in the article Z coordinate and finally, and the seventeenth “Description of Several Chemical Structure File field is the color of the atom. Formats Used by Computer Programs Developed at Molecular Design Limited found in the Journal

Chem & Bio 3D 175 User Guide H0 00 00 H0 00 00 H0 00 00 H0 00 00 H0 00 00 H0 00 00 H0 00 00 H0 00 00 H0 00 00 H0 00 00 1.944 4 2.427 3 0.901 4 - 0.330 9 1 - 0.952 9 1.016 1 0.013 9 1.248 8 - 2.427 3 - 1.758 9 - 0.496 1 2.127 7 - 1.898 1 0.225 0.655 - 0.568 8 7659 - 2.127 7 1.876 1 0.222 7 1.005 4 9 0.010 3 7 4 6 1.261 5 3 6 14 - 15 0.174 16 1.27 - 17 - 18 2.020 19 2.008 20 1.029 21 - 22 0.014 23 0.328 24 125 126 2 127 6 1 128 8 2 129 9 2 0 130 3 0 2 0 0 131 10 0 3 6 0 132 11 0 3 1 1 0 33 4 0 3 1 6 0 34 12 0 0 4 0 0 135 13 1 0 4 1 0 5 0 1 0 14 0 0 0 0 1 6 0 1 0 0 0 0 1 0 0 0 C0 00 00 C0 00 00 C0 00 00 C0 00 00 C0 00 00 C0 00 00 O0 00 00 H0 00 00 1.031 6 1.563 2 0.473 3 - 0.127 7 0.651 8 0.435 9 - 1.756 7 1.857 1 Thisa file describes . 0.194 6 - 0.896 5 - 1.377 7 - 0.204 5 6 0.9011 - 0.426 6 -0.239 0.253 H 0 0 00.561 0 0 7 1.348 8 0.407 2 1 7 3 0.300 7 2.020 7 2.005 1 MDL MACCS-II is a productMDL MDL Infor- of 1 cyclohexanol 2 3 419 19 05- 00 6- 70.562 81.350 90.420 10 -0.559 1.369 11 - 12 - 13 - NOTE: Limited). file cre- sampleMDL MolFile is a The following Pro ated using Chem3D are added cyclohexanol (the line numbers model of foronly): reference of Chemical Information and Computer Science, 3, 1992, pages Number 32, 244–255. Volume mation Systems, Inc. (previouslySystems, mation called Molecular Design, 176

Administrator 36 4 15 1 6 0 0 field is the charge, the seventh field is the stereo 37 5 6 1 1 0 0 parity designator, the eighth field is the number of hydrogens and the ninth field is the center. 38 5 7 1 6 0 0 39 5 16 1 0 0 0 NOTE: Chem3D Pro ignores the following fields: mass 40 6 17 1 0 0 0 difference, charge, stereo parity designator, number of hydro- 41 6 18 1 1 0 0 gens, and center. These fields contain zeros if the file was cre- 42 7 19 1 6 0 0 ated using Chem3D Pro. Each line represents either a blank line, or a data record containing one or more fields of informa- 6. Lines 24–42 (the Bond block) each contain 6 tion about the structure. Each field is delimited by fields which describe a bond in the molecule: the a space(s) or a tab. first field is the from-atom id, the second field is The fields in the MDL MolFile format used by the to-atom id, the third field is the bond type, Chem3D Pro are discussed below: the fourth field is the bond stereo designator, the 1. Line 1 starts the header block, which contains fifth field is an unused field and the sixth field is the name of the molecule. The molecule name is the topology code. the file name when the file was created using Chem3D Pro. NOTE: Chem3D Pro ignores the unused field and topol- 2. Line 2 continues the Header block, and is a ogy code. These fields will contain zeros if the file was created blank line. using Chem3D Pro. 3. Line 3 continues the Header block, and is another blank line. Limitations 4. Line 4 (the Counts line) contains 5 fields which describes the molecule: The first field is the The MDL MolFile format does not support number of atoms, the second field is the number non-integral charges in the same way as Chem3D of bonds, the third field is the number of atom Pro. For example, in a typical MDL MolFile format lists, the fourth field is an unused field and the file, the two oxygens in a nitro functional group fifth field is the stereochemistry. (NO2) contain different charges: -1 and 0. In Chem3D models, the oxygen atoms each contain a charge of -0.500. NOTE: Chem3D Pro ignores the following fields: number of atom lists, the unused field and stereochemistry. These FORTRAN Formats fields will always contain a zero if the file was created using The FORTRAN format for each record of the Chem3D Pro. MDL MolFile format is as follows:

5. Lines 5–23 (the Atom block) each contain 9 Line Description FORTRAN fields which describes an atom in the molecule: Number Format The first field is the X coordinate, the second field is the Y coordinate, the third field is the Z 1 Molecule name A coordinate, the fourth field is the atomic symbol, (file name) the fifth field is the mass difference, the sixth

Chem & Bio 3D 177 User Guide MSI MolFile MSI Thedefined 4, Chapter in is MolFile MSI in the Centrum:“Chem-NoteFile Format” ApplicationChem-Note™ documentation, pages MolFile sample MSI a4-1 to 4-5. is The following cyclohexanol Pro for Chem3D created using file for purposes are added of dis- (the line numbers cussion only): 5I3 3F10.4,1X,A2,5I3 6(1X,I2) 000 0.000 0.000000 0.000 1.000 0.000 Number of bondsNumber of atomic nates, symbol atom, to atom, and bond type 5–23 Atom coordi- 24–42from Bond id, 234 Blank line Blank line Number of atoms 178 1 ! Polygen 133 Polygen 1 ! 23 Polygen Corporation: ChemNote molecule file (2D) 4number version format File * 5 90.0928 6 File * version update number 7 92.0114 8 molecule * name 9 cyclohexanol-MSI 10 formula empirical 11 Undefined Empirical Formula 12 * need 3D conversion? 13 0 14displacement vector * 3D 15 0.000 0.000 0.000 16 matrix * 3D rotation 1.000 0.000 0.000 0.000 1. 1718 * 3D scale factor 19 0 20 * 2D scale factor 21 1 22 * 2D attributes 230 0 0 0 0 0000 1 0 0 0 0 0 * 3D attributes Figure MSI Molfile format E.4: Figure Administrator Figure E.4: MSI Molfile format 24 0 0 0 0 0 0 0 0 0 0 0 25 * Global display attributes 26 1 0 1 12 256 27 * Atom List 28 * Atom# Lbl Type x y x y z bits chrg ichrg frag istp lp chrl ring frad name seg grp FLAGS 29 1 C 10 0 0 -1 0.46 0.2 0 0 0 0 0 0 0 0 0 C 1 0 -1 0 0 0 0 0 0 [C] 30 2 C 10 0 0 1.2 -1.1 0.2 0 0 0 0 0 0 0 0 0 C 2 0 -1 0 0 0 0 0 0 [C] 30 2 C 10 0 0 1.2 -1.1 0.2 0 0 0 0 0 0 0 0 0 C 2 0 -1 0 0 0 0 0 0 [C] 31 3 C 10 0 0 0.1 -1.6 0.7 0 0 0 0 0 0 0 0 0 C 3 0 -1 0 0 0 0 0 0 [C] 32 4 C 10 0 0 1.3 -1.1 0 0 0 0000000C40-1000000[C] 33 5 C 10 0 0 1.2 0.48 0 0 0 0 0 0 0 0 0 0 C 5 0 -1 0 0 0 0 0 0 [C] 34 6 C 10 0 0 0 1.01 -1 0 0 0 0 0 0 0 0 0 C 6 0 -1 0 0 0 0 0 0 [C] 35 7 O 45 0 0 0 2.42 -1 0 0 0 0 0 0 0 0 0 O 7 0 -1 0 0 0 0 0 0 [O] 36 8 H 8 0 0 0.6 2.72 -1 0 0 0 0 0 0 0 0 0 H 7 0 -1 0 0 0 0 0 0 [H] 37 9 H 1 0 0 2.1 0.86 -1 0 0 0 0 0 0 0 0 0 H 8 0 -1 0 0 0 0 0 0 [H] 38 10 H 1 0 0 1.4 0.86 0.8 0 0 0 0 0 0 0 0 0 H 9 0 -1 0 0 0 0 0 0 [H] 39 11 H 1 0 0 1.1 -1.4 -1 0 0 0 0 0 0 0 0 0 H 10 0 -1 0 0 00 00[H] 40 12 H 1 0 0 2.2 -1.4 0.2 0 0 0 0 0 0 0 0 0 H 11 0 -1 0 0 0000 [H] 41 13 H 1 0 0 0 0.72 -2 0 0 0 0 0 0 0 0 0 H 12 0 -1 0 0000 0 [H] 42 14 H 1 0 0 0.1 -2.7 0.7 0 0 0 0 0 0 0 0 0 H 13 0 -1 0 0 0000 [H] 43 15 H 1 0 0 0.3 -1.3 1.7 0 0 0 0 0 0 0 0 0 H 14 0 -1 0 0 0 00 [H] 44 16 H 1 0 0 -1 -1.5 -1 0 0 0 0 0 0 0 0 0 H 15 0 -1 0 0 0000 [H] 45 17 H 1 0 0 -2 -1.5 0.9 0 0 0 0 0 0 0 0 0 H 16 0 -1 0 0 0000 [H] 46 18 H 1 0 0 -1 0.85 1.2 0 0 0 0 0 0 0 0 0 H 17 0 -1 0 0 0000 [H] 47 19 H 1 0 0 -2 0.83 0 0 0 0 0 0 0 0 0 0 H 18 0 -1 0 0 0000 [H] 48 * Bond List 49 * Bond# bond_type atom1 atom2 cis/trans length locked ring Sh_type Sh_nr Qorder Qtopol Qs 50 1 1 1 2 0 0.000 0 0 0 0 [S] 0 0 51 2 1 1 6 0 0.000 0 0 0 0 [S] 0 0 52 3 1 1 18 0 0.000 0 0 0 0 [S] 0 0 53 4 1 1 19 0 0.000 0 0 0 0 [S] 0 0 54 5 1 2 3 0 0.000 0 0 0 0 [S] 0 0 55 6 1 2 16 0 0.000 0 0 0 0 [S] 0 0 56 7 1 2 17 0 0.000 0 0 0 0 [S] 0 0 57 8 1 3 4 0 0.000 0 0 0 0 [S] 0 0

Chem & Bio 3D 179 User Guide The format is YY.MMDD. field this for section. number The format is YY.MMDD. field this for tion. field contains or “Undefined either the file name, Name”. Thiseither the empirical formula field contains Formula”. Empirical or “Undefined from 3D to 2D. cerningconversions 4. Line 4 indicates the file formatnumber. version 5. File update version for the 5 is the header Line 6. number. 6 indicates the file update Line version 7.molecule name sec- for the 7 is the header Line 8. This name. molecule 8 contains the field Line 9. formula.empirical for the 9 is the header Line 10.Line 10 contains the empiricalformula field. contains information11.Lines 11–24 each con- are preceded by a “*”. by are preceded ader line for MSI MolFile at2-cons anglelocked format is broken upinto several 1 are discussed below. are discussed below.

a product of Molecular Simulations, Inc. 1. Molecular Simulations MOLFILE (ChemNote) is format files. created the file. section. number 2. Line 2 normally which application the indicates 3.formatfor the File Line 3 is the header version The for Carbon 6 from the example file field value parentheses for reference: included in is 1.standard he Line 1 is a The MSI MolFile line is either a Each contain a “*”. also Blank lines line a headera data record or containing blank line, fields of informationone or more about the struc- or a space(s) are delimited by fields Individual ture. The fields in the MSI MolFile formattab. file used by Chem3D Pro sections. Section headers sections. 180 7374 * Planarity data 75 area * User data File * End of 5859 14 0 9 1 3 6003 15 10 1 61 1 4 5 0 11 62 0 12 1 4 11 630 13 1 4 12 640 [S] 0 0 000 0.000 14 1 5 6 065 0 0 0 [S] 000 0.000 15 1 5 9 0660 [S] 0 0 000 0.000 0 16 1 5 10 67 0 0 0 [S] 000 0.000 17 1 6 7 068 0 0 0 [S] 000 0.000 0 18 1 6 13 690 [S] 0 0 000 0.000 19 1 7 8 0700 [S] 0 0 000 0.000 Angles * Bond 710 [S] 0 0 000 0.000 * bond1 bond2 angle locked 720 [S] 0 0 000 0.000 * Dihedral Angles 0 [S] 0 0 000 0.000 * at1-cons at1 at2 0 [S] 0 0 000 0.000 Figure format Molfile E.4: MSI Figure Administrator 12.Line 25 is the header for the Global display when the file is created using Chem3D Pro, the attributes section. twenty-seventh field is, again, the atom label (C). 13.Line 26 contains 5 fields describing the global display attributes: Line thickness (1), font style NOTE: Atom types in the Molecular Simulations MolFile (0), type face (1), type size (12), font (256). These format are user-definable. For more information, see “Edit- values are specific to the platform that is gener- ing File Format Atom Types” on page 167. ating the file. 14..Line 27 contains the header for the Atom Lists section. 17.Line 48 contains the header for the Bond List 15.Line 28 contains a listing of all the possible section. fields for the atom list section. When the file is 18.Line 49 contains a listing of all the possible created using Chem3D Pro the following fields fields for the bond list section. When the file is are used: Atom#,Lbl, Type, and x,y,z. created by Chem3D Pro the following fields are 16.Lines 29–47 each contains 28 fields describing used: Bond#, Bond_type, atom 1, atom 2 and information about each of the atoms in the cis/trans and Qorder. structure: the first field is the atom number (6), 19.Lines 50–68 each contain 4 fields describing the second field is the atom label (C), the third information about each of the bonds in the field is the atom type (10), the fourth field and structure: the first field is the internal bond num- fifth fields contain 2D coordinates, and contain ber (6), the second field is the bond type (1), the zeros when the file is created using Chem3D third and fourth fields are the atom serial num- Pro, the sixth field is the X coordinate (-0.113) bers for the atoms involved in the bond [atom 1 and the fifth field is the Y coordinate (1.005), the (2), atom 2 (16)], the fifth field is the cis/trans sixth field is the Z coordinate (-0.675), the sev- designator (this is 0 if it does not apply), the sixth enth through fifteenth fields are ignored and through tenth fields are ignored, and contain contain zeros when the file is created by zeros if the file is created using Chem3D Pro, the Chem3D Pro, the sixteenth field is, again, the eleventh field contains the bond order ([S] mean- atom label (C), the eighteenth field is, again, the ing single), the twelfth and thirteenth fields are atom number (6), the nineteenth field is the seg- ignored and contain zeros if the file is created ment field, the twentieth field is the coordination using Chem3D Pro. field, the twenty first field is ignored, the twenty- 20.Lines 69–73 are each a section header for 3D second field is called the saturation field: if the conversion use. This section only contains the atom is attached to any single, double or delocal- header name only (as shown) when the file is ized bonds this field is 1 (not saturated) other- created using Chem3D Pro. wise this field is 0. The twenty-third through the 21.Line 74 is a header for the section User data twenty-sixth fields are ignored and contain zeros area. This section contains the header name only (as shown) when the file is created using Chem3D Pro. 22.Line 75 is a header that indicates the End of File. FORTRAN Formats

Chem & Bio 3D 181 User Guide 1321 1412 1412 1123 1541 1412 1541 1321 1632 1123 1632 1123 1712 1214 1321 63.950 7 66.020 9 38 55.695 9 178.29 6 2 01 75 178.32 5 172.66 2 81 51 173.03 3 68 09 1- 1176.08 1- 1 55.311 1 64.435 1 57.031 1- 1- 1 64.095 1 62.067 1- 1 -177.17 1 2 1 4 1 65.438 1178.62 1- 16 9 14 2 96 35 04 89 82 85 8 51 26 97 53 1 109.43 1 110.54 1 109.71 1 109.93 1 - 1 111.701 1 109.45 1 110.75 1 110.01 1 107.69 1 109.60 1 107.86 1 106.89 1 110.07 1 109.45 1 109.95 1 109.54 42 99 73 71 97 15 24 64 96 04 39 99 33 66 65 1 H1.115 H1.114 C 1.539 H1.116 C 1.535 H1.116 C 1.534 H1.116 O 1.401 H1.116 H1.117 H 0.941 H1.116 H1.115 H1.116 H1.116 Line 4m: Line 4n: Line 4d: Line 4o: Line 4e: Line 4p: Line 4f: Line 4q: Line 4g: Line 4r: Line 4h: Line 4s: Line 4I: Line 4j: Line 4k: Line 4l: Format I,1X,A,3(1X,I),3F9. 3,1X,I,F4.1,7(1X,I), 1X,A,I,8(1X,I), “[“,A,“ “] I,4(1X,I),F9.3,4(2X ,I),1X, “[“,A1, “] “,2(1X,I) 10 0210 7 10 00 0100 1 111.774 for cyclohexanol:

Description FORTRAN value values 52 23 Cyclohexan ol C0 00C 1.541 00 0000 C 1.535 Line Number 29-47 atom list, field 50-68 field bond list, Line 1: Line 2: Line 3: Line 4a: Line 4b: Line 4c: MOPAC MOPAC by files used Theformat specific of the MOPAC Data-File format. This MOPAC the Chem3D is format is described on pages 1-5 through 1-7 in the and page section in 3-5 MOPAC” “Description of the “GeometrySpecification” section in the further details (fifth edition). For Manual MOPAC format,Data-File please refer about the MOPAC publication. to the above output file sampleMOPAC is a The following fromChem3D The FORTRAN format Thethe FORTRAN of record each for format MolFile Simulations Molecular fol- is as lows: 182

Administrator The following illustrates the components of the The description of the MOPAC Data-File format MOPAC Output File from Chem3D for C(1) for each line is as follows: Through C(4) of Cyclohexanol

Element Bond Action Bond Action Dihedral Action Connectivity Line Description Read by Written Symbol Lengths Integers Angles Integers Angles Integers Atoms Number Chem3D by Chem3D 1st Atom C 0.000000 0 0.000000 0 0.000000 0 000

2nd Atom C 1.541519 1 0.000000 0 0.000000 0 100 1 Keywords for No No

3rd Atom C 1.535233 1 111.774673 1 0.000000 0 210 Calculation Instructions 4th Atom C 1.539734 1 109.711411 11-55.695877 123 2 Molecule Title No Yes 3 Comment No No The internal coordinates section of the MOPAC 4a-s Internal coor- Yes Yes Data-File format contains one line of text for each dinates for atom in the model. Each line contains bond molecule lengths, bond angles, dihedral angles, action integers, and connectivity atoms. 5 Blank line, ter- Yes Yes As shown in the illustration above, C(1) is the ori- minates gin atom. C(2) is connected to C(1) with a bond of geometry defi- length 1.541519 Å. C(3) is connected to C(2) with a nition bond of length 1.535233 Å, and is at a bond angle The FORTRAN format for each line containing of 111.774673 degrees from C(1). C(4) is con- internal coordinate data in the MOPAC Data-File is nected to C(1) with a bond of length 1.539734 Å, FORMAT(1X, 2A, 3(F12.6, I3), 1X, 3I4). and is at a bond angle of 109.711411 degrees from C(2). C(4) also forms a dihedral angle of -55.695877 degrees with C(3). Protein Data Bank Files The action integers listed next to each measure- The Protein Data Bank file format (Protein DB) is ment are instructions to MOPAC which are as fol- taken from pages 3, 14–15, and 17–18 of the Pro- lows: tein Data Bank Atomic coordinate and Biblio- 1Optimize this internal coordinate graphic Entry Format Description dated January, 0Do not optimize this internal coordinate 1985. -1Reaction coordinate or grid index A Protein Data Bank file can contain as many as 32 different record types. Only the COMPND, When you create a MOPAC file from within ATOM, HETATM, and CONECT records are Chem3D, an action integer of 1 is automatically used by Chem3D; all other records in a Protein assigned to each non-zero bond length, bond Data Bank file are ignored. The COMPND record angle, and dihedral angle for each atom record in contains the name of the molecule and identifying the file. information. FORTRAN Formats

Chem & Bio 3D 183 User Guide Z Serial Coord. Number 4th Atom Chem3D Y Serial Coord. Number 3rd Atom X Serial 0.038 -0.962 0.943 Coord. Number 2nd Atom Symbol Serial Element Number 1st Atom File Title Chem3D 21 3 4 8 Column Description Used by Alanine.pdb Serial Serial Number Number CONECT HETATM 1 N COMPND ecord ecord ecord Name Name Name R R R Column Number CONECT 13CONECT 8CONECT 1 9CONECT 2 10CONECT 4 11CONECT 4 12END 4 6 FORTRAN Formats FORTRAN Theof the COMPND record for- description full as follows: files is mat in Protein Data Bank The ATOM or HETATM record contains the record or HETATM The ATOM the of the serial number by followed record name, atom being described, element the that for symbol Z Cartesian and coordinates thenatom, the X, Y, for that atom. A CONECT record is the atomic used to describe The contain the records CONECT connectivity. the of the serial number by followed record name, described, then is being atom whose connectivity of the first atom, second atom, the serial numbers third atom fourth and atom the described to which atom is connected. Alanine.pdb The COMPND record is created Chem3Dby to COMPN D HETATM 1HETATM 2HETATM N 3HETATM C 4HETATM 0 C 5HETATM 0 C 6 -0.962HETATM 0.6 1 O 7 -0.049HETATM -2 0 O 0.834 13HETATM -1 0.3 H 8 0.834HETATM H 1.8 1 1.737 9HETATM -1 0.9 0.459 H 10 -1HETATM 0 H -1.398 11 1 HETATM H -1 -1.737 12 1 CONECT12713 -2 H -0.642 -1CONECT21348 H -1 1.564CONECT3256 -2 0 1.41 2.4CONECT4291011 1 0.211CONECT 1.06 5 1 CONECT -1 6CONECT 3 7 3 1 12 is not used when opening a file. opening is not used when TheData is an example of a Protein following L-Alanine. Output File from Chem3D for Bank NOTE: The ATOM record contains atomic coordinate coordinate atomic contains record The ATOM HETATM and the groups, “standard” for records for records coordinate atomic record contains record The CONECT groups. “non-standard” records. atomic connectivity contains the include the title of a Chem3D model only when you areinclude the title of a Chem3D model you only when saving file the using Proteina Data Bank fileformat. This record 184

Administrator 1-6 Record Name (COM- Yes 47–54 Z Orthogonal Å Yes PND) coordinates 7-10 UNUSED No 55–60 Occupancy No 11-70 Name of Molecule Yes 61–66 Temperature Factor No The full description of the ATOM and HETATM 67 UNUSED No record formats in Protein Data Bank files is as follows: 68–70 Footnote Number No The full description of the CONECT record format in Protein Data Bank files is as follows: Column Column Description Used by Number Chem3D Column Column Description Used by 1-6 Record Name Yes Number Chem3D (HETATM or ATOM) 1–6 Record Name Yes 7-11 Atom Serial Number Yes (CONECT) 12 UNUSED No 7–11 Atom Serial Number Yes 13–16 Atom Name (Ele- Yes 12–16 Serial Number of First Yes ment Symbol) Bonded Atom 17 Alternate Location No 17–21 Serial Number of Sec- Yes Indicator ond Bonded Atom 18–20 Residue Name Optional 22–26 Serial Number of Yes Third Bonded Atom 21 UNUSED No 27–31 Serial Number of Yes 22 Chain Identifier No Fourth Bonded Atom 23–26 Residue Sequence No 32–36 Hydrogen Bonds, No Number Atoms in cols. 7–11 are Donors 27 Code for insertions of No residues 37–41 Hydrogen Bonds No 28–30 UNUSED No 42–46 Salt Bridge, Atoms in No cols. 7–11 have Nega- 31–38 X Orthogonal Å Yes tive Charge coordinates 39–46 Y Orthogonal Å Yes coordinates

Chem & Bio 3D 185 User Guide -Feb-1987. The following -Feb-1987. 00000 05-MAY- Chem3D Cyclohexane Line 1 >STRT Line2 DTCR 92 12:32:26 Line 3Line 4 >CT Cyclohexan 00039 Line 5 19 19 (A2,5I2) (6I3) Line 6 C Line 7 C 0Line 8 C Line 9 0 C 0Line 0 10 C C 0Line 11 0 H 0Line 0 12 0 0 H Line 0 13 0 0 H Line 0 14 0 0 0 H Line 15 0 0 0 H Line 16 0 0 0 O 0 Line 17 0 0 H 0 Line 18 0 0 H 0 Line 19 0 0 H 0 Line 20 0 0 H 0 Line 21 0 0 H 0 Line 22 0 0 0 H Line 23 0 0 H 0 Line 24 0 0 1 0 Line 25 0 0 1 0 Line 26 0 1 0 2Line 27 0 1 0 6Line 28 2 0 12 1 Line 29 2 0 14 1 Line 30 1 2 3 1 7 15 1 1 1 documentation, dated 04 Pro Chem3D using produced file SMD sample is a for added are (the line numbers for cyclohexanol purposes only). of discussion format file SMD E.5: Figure No No file formatis 1 SMD file) file for- SMD file) file 2 1X, A3,10X, 3F8.3,16X I5,1X,A4,14X,3F8.3,16X Atoms in colsAtoms are 7–11 Acceptors cols. 7–11 have Posi- have 7–11 cols. Charge tive 1. Rosdal is a product of Softron, Inc. Softron, of a product is Rosdal 1. AG. Bayer AV-IM-AM Bebak H. - format SMD 2. 47–51 Hydrogen Bonds, 52–5657–61 Hydrogen BondsAtoms in Salt Bridge, No COMPNDATOM 4X, 60A1 ‘COMPND’, 2X, I5,1X,A4, ‘ATOM’, Line Description Format FORTRAN HETATMCONECT ‘HETATM’, 30X ‘CONECT’, 5I5, mat is defined in the 4.3 SMD File Format version defined in Appendix C: Rosdal Syntax, defined inpages Appendix C: Rosdal TheManual. 91–108, of the MOLKICK User’s formatRosdal primarily used for query is searching formatin the BeilsteinRosdal Online Database. is a sample Thefollowing files are for export only. formatRosdal file created using Chem3D Pro for cyclohexanol: 1-2-3-4-5-6,1-6,2-7H,3-8H,4-9H,5-10H,6-11H,1- 12O-13H,1-14H,2-15H, 3-16H,4-17H,5-18H,6- 19H.@ The Standard Molecular Data SMD ROSDAL Structure The Rosdal Language The FORTRAN formatsThe FORTRAN for the records used in file format the Protein Data Bank are as follows: 186

Administrator Figure E.5: SMD file format mation about the structure. The SMD file is bro- Line 31 3 4 1 ken down into several blocks of information. The header for each block starts with a > sign. Individ- Line 32 3 8 1 ual fields are delimited by space(s) or a tab. Line 33 3 16 1 The fields in the SMD format file used by Line 34 4 5 1 Chem3D Pro are discussed below: Line 35 4 9 1 1. Line 1 starts the block named STRT. This block Line 36 4 17 1 contains the molecule name. The molecule name Line 37 5 6 1 is the file name when the file was created using Line 38 5 10 1 Chem3D Pro. Line 39 5 18 1 2. Line 2 starts the block named DTCR. The infor- Line 40 6 11 1 mation in this line includes the name of the application that created the file and the date and Line 41 6 19 1 time when the file was generated. Line 42 12 13 1 3. Line 3 starts the block named CT which contains Line 43 >CO ANGSTROEM 0020 the connection table of the compound(s). Also Line 44 4 (3I10) on this line is a 10 character description of the Line 45 -6903 13566 -4583 connection table. This will be the same as the file Line 46 -14061 808 125 name when the file is generated using Chem3D Pro. Finally, the number of records contained Line 47 -4424 -8880 7132 within the CT block is indicated, 39 in the above Line 48 7577 -12182 -1855 example. Line 49 14874 594 -6240 4. Line 4 of the CT Block contains four fields. The Line 50 5270 10234 -13349 first field is the number of atoms, the second Line 51 -18551 -4300 -8725 field is the number of bonds, the third field is the Line 52 -9815 -18274 9852 FORTRAN format for the number of atoms, and the fourth field is the FORTRAN format Line 53 4047 -17718 -10879 for the number of bonds. Line 54 19321 5600 2685 5. Lines 5–23 of the CT Block each contain 4 fields Line 55 10636 19608 -16168 describing an atom. The first field is the element Line 56 -2794 21139 6600 symbol (first letter uppercase, second lowercase). Line 57 2876 15736 11820 The second field is the total number of hydro- Line 58 -14029 20018 -10310 gens attached to the atom, the third field is the stereo information about the atom and the Line 59 -22477 3450 6965 fourth field is the formal charge of the atom. Line 60 -806 -4365 16672 Line 61 14642 -18918 3566 NOTE: If the file is created using Chem3D Pro, the num- Line 62 23341 -2014 -13035 ber of hydrogens, the stereo information and the formal charge Line 63 1740 5536 -22837 fields are not used, and will always contain zeros. Each line is either a blank line, a block header line or a data record containing multiple fields of infor-

Chem & Bio 3D 187 User Guide - 0.5185 C 0.5913 C 0.7800 C 0.7768 C - 0.7007 O - 1.5689 H - 1.6577 H 0.1228 H - 0.4983 H - 1.3895 H 1.4669 H 0.5742 H 1.7389 H - 0.0419 H 0.8816 H 37 0.47 7 1.32 4 0.44 5 38 0.34 3 36 41 2 0.31 4 2 1.16 1 1.89 3 2.07 6 1.08 1 3 1 -1.473 0.37 4 1 1.1286 - 51-0.139- 61-1.396- 7 8 2.1708 1.22 8 13 1.0068 - 9 13 -0.284 1.79 10 13 -0.147 1.97 11 13 -2.375 1.03 12 13 -1.589 - 13 13 1.2546 0.20 14 13 2.0091 - 15 13 -0.077 - 16 13 -0.21 - 17 13 -2.308 - - 0.7007 C - 0.7007 C Also in this line is the 81 38 1989 SYBYL Programming Man- Cyclohexa nol0 MO L 1 1 1.0682 0.35 1 -0.207 1.22 . number of lines 20 in in the block, example. this number the coordi- used to convert tains the exponent to the coordinate nates in the lines following 43. Thetype specified in line the second field is format FORTRAN of the atom coordinates. the Cartesianatomindicatedan coordinates of Theis the X coordi- field block. first in the CT coordinate and the the second field is the Y nate, Z coordinate. the is third field fields describing a bond between the two atoms. atoms. the describing fields two bond between a atom the of The number is the serial first field the second the bondis field starts, which from where the bond ends, of atom number the serial bond order. third field is the the and Cartesianthe coor- includes block mation in this and CT block the from atoms all the of dinates indicates the type of coordinates used, Ang- stroms in this example. 1 9 SYBYL MOL File MOL SYBYL The SYBYL MOL File format (SYBYL) is defined in ChapterFormats”, pages 9, “SYBYL File 9–1 through 9–5, of the ual SYBYL in is an example of a file The following This file format producedfrom within Chem3D. cyclohexanol. of a model describes 8. Thefirst field con- fields. Line 44 containstwo 9.fields describing three contains each Lines 45–65 6. 3 contains each Block of the CT Lines 24–42 7. The infor- Line 43 starts named CO, the block 188

Administrator 18 13 -1.372 0.24 1.6545 The following illustration shows the components 42 H of the SYBYL Output File from Chem3D for C(6) 19 13 2.9386 0.68 - and Bond 3 of Cyclohexanol. 91 0.8100 H 1 MO 9 L Number Molecule of Atoms Name Center 112 1 19 MOL Cyclohexanol 0 214 1 6 1 -1.3959 -0.4449 0.7768C 317 1 Atom Atom X Y Z 418 1 ID Type Coord Coord Coord Number 523 1 of Bonds 629 1 19 MOL

72101 31 7 1 836 1 Bond From-Atom To-Atom Bond 93111 Number Type Number 10 3 12 1 of Features 11 4 5 1 0 MOL 12 4 13 1 13 4 14 1 14 5 6 1 15 5 15 1 The format for SYBYL MOL files is as follows: 16 5 16 1 1. The first record in the SYBYL MOL File con- 17 6 17 1 tains the number of atoms in the model, the word “MOL”, the name of the molecule, and the 18 6 18 1 center of the molecule. 19 7 19 1 2. The atom records (lines 2–20 in the cyclohex- 0MO anol example) contain the Atom ID in column 1, L followed by the Atom Type in column 2, and the X, Y and Z Cartesian coordinates of that atom in columns 3–5. 3. The first record after the last atom records contains the number of bonds in the molecule, followed by the word “MOL”. 4. The bond records (lines 22–40 in the cyclohexanol example) contain the Bond Number in column 1, followed by the Atom ID of the atom where the bond starts (the “From-Atom”) in column 2 and the Atom ID of the atom where

Chem & Bio 3D 189 User Guide H H H H H C.3 C.3 C.3 C.3 H C.3 H C.3 0.65 5 0.9 H - 0.33 1 2.42 7 1.94 4 0.25 3 6 0.65 2 - 0.12 8 0.47 3 - 1.01 6 1.56 3 - 0.95 3 1.03 2 0.56 5 2.12 8 1.89 8 0.49 6 1.75 9 0.23 9 0.20 5 1.37 8 6 0.89 6 9 5 13 H 2.008 - 12 H 2.021 0.22 1011 H 1.27 - H -0.01 - 9 H 0.175 - 8 H -1.005 - 7 H -2.021 - 6 C -0.559 1.37 0.43 5 C 0.42 0.9 - 4 C 1.351 - 3 C 0.562 - 14 H 1.03 1.76 2 C -0.407 - @ATOM 1 C -1.349 0.19 Line Line 23 Line Line 22 Line Line 20 Line 21 Line Line 19 Line Line 18 Line Line 17 Line Line 16 Line Line 15 Line Line 14 Line Line 13 Line Line 24 Line Line 12 Line 7Line NO_CHARGES 8 Line 9 Line Line 10 Line 11 Figure E.6: SYBYL MOL2 file format file MOL2 SYBYL E.6: Figure

The The nd records is thend records bond is I4,1X,'MOL',20A2,11 X,I4 I4,1X,'MOL' file format file (SYBYL2) is Thisfile describes a modelof 1 . 1991 SYBYL ProgrammingManual. HEXANOL ECULE subsidiary of Evans & Sutherland. 1. SYBYL is a product of TRIPOS Associates, Inc., a the bond stops (the “To-Atom”) in column 3. in column the bond “To-Atom”) stops (the The last bo in the column use this information.does not type. Finally Finally the last line in the type. file is the Number number the contains record, which Features of Chem3D of feature in the molecule. records Line DescriptionNumber of Atoms/File Name Format FORTRAN recordsAtom Number of Bonds record I4,1X,'MOL' Bond records 2I4,3F9.4,2A2 Number of Features record 3I4,9X,I4 Line 1Line Name: CYCLO- # Line 2 Line 3 @MOL- Line 4 CYCLOHEXANOL Line 500 19 19 0 Line 6 SMALL Figure E.6: SYBYL MOL2 file format MOL2 SYBYL E.6: Figure SYBYL MOL2 File MOL2 SYBYL MOL2 SYBYL The The FORTRAN format The the FORTRAN record of each for SYBYL MOL File formatas follows: is FORTRAN Formats FORTRAN following is a sample SYBYL MOL2 file created is following Chem3D Pro using defined in Chapter 3, “File Formats”, pagesin defined 3033– the 3050, of for refer- added are cyclohexanol (the line numbers ence only): 190

Administrator Figure E.6: SYBYL MOL2 file format Figure E.6: SYBYL MOL2 file format Line 15 O -0.3 0.42 - O.s Line 16 5 15 1 25 7 1.75 p 46 7 Line 17 6 16 1 Line 16 H -1.262 2.12 0.01 H 47 26 8 4 Line 18 6 17 1 Line 17 H 0.014 1.87 1.24 H 48 27 6 9 Line 19 15 19 1 Line 18 H -2.005 0.56 1.85 H 49 28 2 7 Each line is either a blank line, a section header or Line 19 H 0.329 0.22 - H.s a data record containing multiple fields of informa- 29 3 2.42 p tion about the compound. The SYBYL MOL2 file 7 is broken down into several sections of informa- Line @BOND tion. Record type indicators (RTI) break the infor- 30 mation about the molecule into sections. RTI’s are Line 13121 always preceded by an “@” sign. Individual fields 31 Line 2161 are delimited by space(s) or a tab. 32 The fields in the SYBYL MOL2 format file used Line 3171 by Chem3D Pro are as follows: 33 Line 41181 1. Line 1 is a comment field. The pound sign pre- 34 ceding the text indicates a comment line. Name: Line 5231 is a field designating the name of molecule. The 35 molecule name is the file name when the file is Line 6281 created using Chem3D Pro. 36 2. Line 2 is a blank line. Line 7291 3. Line 3, “@MOLECULE”, is a 37 Line 8341 Record Type Indicator (RTI) which begins a sec- 38 tion containing information about the mole- Line 93101 cule(s) contained in the file. 39 Line 10 3 11 1 NOTE: There are many additional RTIs in the SYBYL 40 Line 11 4 5 1 MOL2 format. Chem3D Pro uses only @MOLECULE, @ATOM and Line 12 4 12 1 @BOND. 42 Line 13 4 13 1 43 4. Line 4 contains the name of the molecule. The Line 14 5 6 1 name on line 4 is the same as the name on line 1. 44 5. Line 5 contains 5 fields describing information Line 15 5 14 1 about the molecule: The first field is the number 45 of atoms, the second field is the number of bonds, the third field is the number of substruc-

Chem & Bio 3D 191 User Guide Format “# “,5X, “Name: “,1X,A 4(1X,I2) I4,6X,A2,3X, 3F9.3,2X,A5 3I4,3X,A2 BOND”, is a Record a Record BOND”, is name) Description FORTRAN atoms/number of atoms/number bonds coordinatesand id to-atom, bond type Atom types areAtom types See “Editing File user-definable Type Indicator (RTI) which begins a section which Indicator(RTI) Type containing information about the associ- bonds with the molecule. ated informationthe field is about a bond: the first the from-atom id, the is second field the bond id, to-atom id, and the fourththe third field is field is the bond type. the Y coordinate, the fifth field is the Z coordi- is the Z fifth field the coordinate, the Y type. atom and the sixthnate the field is Line Number 1 Molecule (file name 5 Number of 11–29 name, Atom type, 31–49from-atom, Bond id, FORTRAN Formats FORTRAN format The FORTRAN record of the each for File formatSYBYL MOL2 follows: is as NOTE: creating or ifying atom type. an 12.Line 30, “@ containfields describing4 13..Lines 31–49each Format Atom Types” on page 167 for instructions 167 for on page on mod- Atom Types” Format . . Four asterisks appear in line 8 when therearein line 8 when asterisksappear no Four Chem3D Pro ignores number the following fields: tures, the fourth of field tures, features number is the sets. of number is the fifth field the and Type Indicator (RTI) which begins a section which (RTI) Indicator Type containing informationthe atoms of abouteach associated with the molecule. informationfirst fieldthe about an atom: the is the the atom name, second field is the atom id, the fourththird field is the X coordinate, field is contains SMALL if the file is created using is created SMALL if the file contains Chem3D Pro the molecule. This contains field the molecule. using is created file if the NO_CHARGES Chem3D Pro tain internal associated with SYBYL status bits the molecule. with the molecule. tain comments associated NOTE: in Line 9. is a Record 10.Line10, “@ATOM”, contain 6 fields describing 11.Lines11–29 each NOTE: Chem3D Pro. 6.This molecule field the type. Line 6 describes 7. Line 7 describes the charge type associated with 8.might con- example, Line 8, blank in the above 9.might con- example, 9, blank in the above Line status bits associated with the molecule but therestatus bitsassociatedthe with comment is a of substructures, features number of number of sets. and will contain zeros These fields createdusing was the file if 192

Administrator Export File Formats File Format Name Extension The following table shows all of the chemistry file formats that Chem & Bio 3D 11.0 supports. MSI ChemNote MSI ChemNote .msm MOPAC input MOPAC .mop; .dat; File Format Name Extension file .mpc; 2mt MOPAC graph .gpt Alchemy Alchemy .alc; .mol file Cartesian Coordi- Cart Coords 1 .cc1 Protein Data Protein DB .pdb; .ent nate Bank Cart Coords 2 .cc2 ROSDAL Rosdal .rdl CCDB Cambridge Crys- .ccd Standard Molecu- SMD File .smd tallographic lar Data Database SYBYL MOL SYBYL .sml Chem3D .c3xml; .c3d SYBYL MOL2 SYBYL2 .sm2; .ml2 Chem3D tem- .c3t plate To save a model with a different format, name or location: ChemDraw ChemDraw .cdx; .cdxml 1. Go to File>Save As. The Save File dialog box Connection Table Conn Table .ct; .con appears. GAMESS Input GAMESS Input .inp 2. Specify the name of the file, the folder, and disk where you want to save the file. Gaussian Check- .fchk; .fch 3. Select the file format in which you want to save point the model. Gaussian Cube .cub 4. Click Save. When you save a file in another file format, only Gaussian Input Gaussian Input .gjc; .gjf information relevant to the file format is saved. For Internal Coordi- Int Coords .int example, you will lose dot surfaces, color, and atom nates labels when saving a file as an MDL MolFile. MacroModel MacroModel .mcm; .dat; Publishing Formats .out The file formats described in this section are avail- Maestro Maestro *.mae able for importing and exporting models as pictures. The pictures can then be used in desktop Molecular Design MDL MolFile .mol publishing and word processing software. Limited MolFile Image Format Features

Chem & Bio 3D 193 User Guide PS). EPS files are ASCII Chem & Bio 3D 11.0 does not embed structural 11.0 does not embed 3D Chem & Bio EPS as encap- file format models The saves PostScript sulated postscript file (E repre-text files containing the scalable PostScript sentation of a Chem3D can open EPS picture. You files using other as PageMaker. applications such can transfer EPS among files platforms, You and UNIX. including Macintosh, Windows, TIF The TaggedImage (TIFF) contains Format File binary data describingimagea bitmap of the high resolution formatmodel. TIFF is a commonly graphicsused for saving for cross-platform importing desktop into publishing applications. of resolu- variety a using images be saved can TIFF As TIFF and compression options. tion, color, images can get appropriate large, choosing options is important. NOTE: Bio 3D 11.0. BMP The Bitmap file format repre- the bitmapped saves sentation of a Chem3D The Bitmap file picture. format to transfer Chem3Dyou enables pictures for Microsoft Word as such to other applications, that support bitmaps. Windows, information have If you models exported in files. as EMF files producedEMF open can still with previousyou versions, them in Chem & Bio 3D 11.0and work with the structure. However, savedfiles EMF from 8.0 contain Chem3D graphic information only opened in Chem and cannot be & EMF files are exported files EMF back- transparent with supported this is when grounds, the operating by system (Windows 2000 and Windows XP). The formatsEMF file WMF and are supported by for Windows. as Microsoft Word applications such n Save tab of tab of the 1 Pictures Set JPEG compressio Set JPEG the clipboard, and the clipboard, Transparent background and Transparent animation support Set resolution zolato 1. CxImage: Copyright © 2001 - 2004, David Piz- David - 2004, © 2001 Copyright CxImage: 1. File menu command or command File menu page TIFF, or AVI formats. formats. or AVI page TIFF, from 0 to 100%. •multi- GIF, in animated saved can be Movies • OLE copy/paste Transparent • bitmap imagesto DPI. 1200 up Save • Quality JPEG can be adjusted (compression) Theset in the new are defaults As... Chem3D supports the Windows Metafile and Chem3D supports Windows the Enhanced Metafile file formats. These are the only graphic formats (as opposed to chemistry modeling formats) that can be used for import. They may the using export,for also be used by EMF Graphic file formatting uses CxImage©, an open zlib license. the source toolset under WMF and EMF Figure E.7: Save as GIF dialog box as GIF dialog E.7: Save Figure Chem3D 11 gives you more options when saving saving when options more you 11 gives Chem3D set graphicto easier are options and the formats, than ever. WMF by using the clipboard using the clipboard (only). See “Using the by WMF Clipboard” on page information. 105 for more Preferences dialog box. the available displays now dialog box The Save when defaults easier to override it make to options, you save. 194

Administrator When you save a file as TIF, an option button 4. Choose a compression option: appears in the Save As dialog box. To specify the save options: If you want to … Then choose … 1. Click Options. reduce file size by encod- PackBits. Figure E.8: The TIFF Options dialog box ing repeating bytes of information as output. For example, for a line of color information such as: CCCCC- MMMMMYYYYYKKKK K, the compression yields 2. Choose a resolution. The size of the file a smaller file by represent- increases as the square of the resolution. ing the information as 3. Choose a color option. C5M5Y5K5.

fax transmissions of CCITT Group 3 or If you want to … Then choose … images CCITT Group 4.

force objects to Monochrome. GIF, PNG and JPG black and white. Use the Graphics Interchange Format (GIF), Por- store colors using RGB Indexed. table Network Graphics (PNG) file format, or the computer monitor JPEG format to publish a Chem3D model on the style of color encod- world wide web. Each of these formats uses a com- ing. pression algorithm to reduce the size of the file. Applications that can import GIF, PNG, and JPG CMYK Contiguous. use printing press files include Netscape Communicator and style of color encod- Stores colors non-sequen- Microsoft Internet Explorer. ing. tially. For example: The model window background color is used as CMYKCMYK. The Pack- the transparent color in the GIF format graphic. Bits compression type provides no compression for this type of file. NOTE: The size of the image in Chem3D when you save the file will be the size of the image as it appears in your web page. If you turn on the “Fit Model to Window” building NOTE: If objects in your document are black and white preference in Chem3D, you can resize the Chem3D window they are saved as black and white regardless of which Color (in Chem3D) to resize the model to the desired size then options you set. If you import drawings from other applica- save. tions and want them to print Black and White you must set the Color option to Monochrome. 3DM The QuickDraw 3D MetaFile (3DM) file format contains 3-dimensional object data describing the

Chem & Bio 3D 195 User Guide Save All Frames. By Serial Number. By Position. Missing. Include Serial Num- bers. Include Atom Type Text Numbers. . The Connection Table Options . The Connection Table Options dialog box appears. dialog box contain internal coordinates view of the model for each If you want the fileto … contain a connectiontable for Then click … serial num- atom with each bers contain a connection table for adja- that describes atom each their positions cent atoms by in the file notcontain a connection table contain serial numbers contain type numbers atom Connection Table ordersbond Chem3D uses the atom symbols and of connection table files to guess the atom symbols There are two ordersbond of the atom types. and Theconnection table file formats, CT and CON. formatCON supported is only for import. an as a Connection Table, a file save When you box. dialog As Save the Options button appears in options: specify the save To 1. Click box dialog Options Table The Connection E.10: Figure 2. appropriate Select the options: Coordinates Options dialog Coordinates . The Cartesian Coordinates Options Options dialog box appears. Options dialog box box Figure E.9: The Cartesian Figure Cartesian Coordinates Use Cartesian Coordinates 1 (.CC1) or 2 (.CC2) to and Z Cartesian coordi-import or export the X, Y, model. your nates for an a file as Cartesian Coordinates, save When you As dialog box. optionSave thein button appears options: specify the save To 1. Click Alchemy formatALC file Use the TRI- with to interface This as is sup- Alchemy©. POS© applications such ported only for input. Export Formats file formatsThe following to export are used models to chemistry modeling application other than formats11.0. Most of the Chem & Bio 3D also support import. AVI cre- have you format file a movie this Use to save importcan the model. You active ated for the application that sup- into any file resulting movie file format. ports the AVI model. You can import can many 3D files into 3DM You model. files transfer can 3DM You modeling applications. platforms. Macintosh and Windows between 196

Administrator 2. Select the appropriate options: tains information related to grid data and model coordinates. Gaussian Cube files are supported for If you want to add … Then click … import only. Chem3D displays the surface the file describes. If a blank line to the top of 1 Blank Line. more than one surface is stored in the file, only the the file first is displayed. You can display additional surfaces using the Surfaces menu. two blank lines to the top 2 Blank Lines. of the file Internal Coordinates

three blank lines to the top 3 Blank Lines. Internal Coordinates (.INT) files are text files that of the file describe a single molecule by the internal coordinates used to position each atom. The serial num- Gaussian Input bers are determined by the order of the atoms in the file. The first atom has a serial number of 1, the Use the Gaussian Input (GJC, GJF) file format to second is number 2, and so on. Internal Coordi- interface with models submitted for Gaussian cal- nates files may be both imported and exported. culations. Either file format may be used to import You cannot use a Z-matrix to position an atom in a model. Only the Molecule Specification section terms of a later-positioned or higher serialized of the input file is saved. For atoms not otherwise atom. If you choose the second or third options in specified in Chem3D, the charge by default is writ- the Internal Coordinates Options dialog box, the ten as 0, and the spin multiplicity is written as 1. nature of the serialization of your model deter- You can edit Gaussian Input files using a text edi- mines whether a consistent Z-matrix can be con- tor with the addition of keywords and changing structed. If the serial numbers in the Z-matrix optimization flags for running the file using the which is about to be created are not consecutive, a Run Gaussian Input file within Chem3D, or using message appears. You are warned if the atoms in Gaussian directly. the model must be reserialized to create a consis- Gaussian Checkpoint tent Z-matrix. A Gaussian Checkpoint file (FCHK; FCH) stores When you click Options in the Save As dialog box, the results of Gaussian Calculations. It contains the the following dialog box appears: final geometry, electronic structure (including Figure E.11: The Internal Coordinates Options dialog box energy levels) and other properties of the molecule. Checkpoint files are supported for import only. Chem3D displays atomic orbitals and energy levels stored in Checkpoint files. If Cubegen is installed, molecular surfaces are calculated from the Check- point file. Gaussian Cube A Gaussian Cube file (CUB) results from running Cubegen on a Gaussian Checkpoint file. It con-

Chem & Bio 3D 197 User Guide command Frames check box to create a box check Frames

Run MOPAC Input file Run MOPAC All

MOPAC Files MOPAC MSI ChemNote within Chem3D. As dialog box, Options in the Save click When you appears: Options dialog box the MOPAC MPC, DAT, be stored in MOP, data may MOPAC or 2MT file formats. can importChem3D any of You these file formats, and can export MOP files. adding files using a text editor, can editMOPAC optimization and and changing run flags, keywords the file using the box dialog options The MOPAC E.12: Figure the Save Click Molecular Design Limited MolFile Limited Design Molecular MDL Thefiles by Molfile format MDL saves ISIS/Base, as ISIS/Draw, applications such The file format is defined and REACCS. MAACS Chemical in the article,Several of “Description Structure Computer Pro- Used by File Formats grams Design Limited” at Molecular in Developed Information of Chemical the Journal and Com- 32, Number 3, 1992, pages Volume puter Science, 244–255. ISIS formatthis Use MDL’s to interface with other chemistry-relatedapplications and applica- Both importexport and tions. are supported. file format ChemNote (.MSM) MSI the Use to applications Simulations interface with Molecular The file format as ChemNote. such is defined in the ChemNote Both importdocumentation. and export are supported. MOPAC Data file in which the internalthe coordi- Data file in which MOPAC . University, New York, York, New University, The Pro-R and The and Pro-S Pro-R des- stereochemical ignationsnot are used in constructing a Z-matrix from the model. All atoms are dihe- positioned by dral angles only. Pro-R/Pro-S and are Dihedral angles used to position atoms. Only Serial Numbers; Dihedral Angles Only Use Current Z-matrix. Current Use Only Serial Numbers; Bond and Dihedral Angles. (MCM; DAT; OUT)file for- (MCM; DAT; 1 of Chemistry at Columbia of Chemistry N.Y. 1. MacroModel is produced within the Department build a Z-matrix in the current serial which of the ordering number atoms in the model is preserved the Z- in matrix build a Z-matrix in the current serial which of the ordering number is atoms in the model preserved in the Z- matrix If you want to … to you want If using model your save … click Then described the Z-matrix in the Internal Coordi- modelthe nates table of mats are defined in the MacroModel Structureare mats documentation. 2.0 Chem3D sup- Files version ports and can export import file types, all three of MCM Maestro Files 11.0Chem & Bio 3D supportsSchrodingerthe Maestro file format(MAE)for importing and exporting molecular models. MacroModel Files The MacroModel Select theSelect appropriate options: 198

Administrator nates for each view of the model are included. The C 1.539 1 109. 1 -55.6 1123 L7.L initial frame of the model contains the first 3 lines 73 7 9 of the usual MOPAC output file (see the example n file below). Each subsequent frame contains only lines describing the Z-matrix for the atoms in that Ln+ frame. 1 2. In Line 1, type the keywords for the computa- NOTE: For data file specifications, see page 13 of the tions you want MOPAC to perform (blank in the online MOPAC manual. example above). Line 2 is where enter the name that you want to assign to the window for the resulting model. However, Chem3D ignores this To edit a file to run using the Run MOPAC Input line. File command: 3. Leave Line 3 blank. 1. Open the MOPAC output file in a text editor. 4. Line 4 through Ln (were n is the last atom The output file below shows only the first four record) include the internal coordinates, optimi- atom record lines. The first line and column of the zation flags, and connectivity information for the example output file shown below are for purposes model. of description only and are not part of the output • Column 1 is the atom specification. file. • Column 2 is the bond distance (for the connectivity specified in Column 8). Col. Col. 2 C Col. C Col. Col. Col. • Column 3 is the optimization flag for the 1 3 4 5 6 7 8 bond distance specified in Column 2. • Column 4 is the bond angle (for the connec- Line tivity specified in Column 8). 1 • Column 5 is the optimization flag for the bond angle specified in Column 4. Cyclohexanol Line • Column 6 is the dihedral angle (for the con- 2 nectivity specified in Column 8). • Column 7 is the optimization flag for the Line dihedral angle specified in Column 6. 3 5. To specify particular coordinates to optimize, C 0 00 00 0 000 Line change the optimization flags in Column 3, Col- 4 umn 5 and Column 7 for the respective internal coordinate. The available flags in MOPAC are: C 1.541 10 00 0 100 Line 5 52 1 Optimize this internal coordinate C 1.535 1 111. 10 0 210 0 Do not optimize this internal Line 23 77 6 -1 Reaction coordinate or grid index

Chem & Bio 3D 199 User Guide (SML, SM2, ML2) file formats (SML, SM2, to © Standard Molecular Data (SMD) Data (SMD) Molecular Standard JDF Files The JDF file format is a file format job for saving can you a JDF file, open Whenyou descriptions. the settings. save CSBR and edit JDT Files The JDT file formatis a template format for sav- can be applied to future calcula- settings that ing can edit the settings of a template file, You tions. changes. your cannot save you however Standard Use the (.SMD) Data for- file Molecular interfacingapplica- the STN Express with mat for Both database searching. for online tion chemical importexport and are supported. Files SYBYL Use the SYBYL File Formats Job Description custom- description filessave to use Job can You can save You ized default settings for calculations. Description file customized calculations as a Job Description Stationery(.JDF) or Job (.JDT). Sav- formateither ing to job folder adds it Chem3D in a the appropriate Chem3D menu. interface with Tripos’s SYBYL applications. The SYBYL applications. interface with Tripos’s formatsSML and SM2 for bothcan used be importexport; and the ML2 format is supported for import only. . (RDL) file for- 1 The ROSDAL ROSDAL The . 1. ROSDAL is a product of Softron, Inc. Softron, of ROSDAL is a product 1. example, symmetryexample, informationSAD- in a used DLE computation. cate file termination. T Monitor turning DRC points in ROSDAL Files (RDL) formatused for query is primarily in the searching supports Chem3D Beilstein Online Database. the format file for export only ROSDAL mat is defined in Appendix C: ROSDAL Syntax of mat is defined in Appendix ROSDAL C: manual this and in Manual, the MOLKICK User’s in Appendix E, “File Formats.” Structure Language The ROSDAL Protein Data Bank Files Protein Data Bank Protein Data Bank (PDB; ENT) files Brookhaven to store protein data and are typically largeare used Chem3D and import can in size. both types, file TheformatPDB file from exportstaken is PDB. the ProteinAtomic Coordinate Data Bankand BibliographicEntry Description. Format MOPAC Graph Files Graph MOPAC Graph stores (GPT) file of results the A MOPAC that include the GRAPH calculations MOPAC electronic the final geometry, It contains keyword. structure, and other properties molecule. of the file format Graph Chem3D supports MOPAC the for import only. 6. information Add additional line Ln+1. For in 7.indi- to in the data file blank last line the Leave 8.format. only a text the file in Save 200

Administrator Appendix F: Parameter Tables

Chem3D uses the parameter tables, containing Bond Stretching Parameters. Standard bond information about elements, bond types, atom lengths. In force field analysis, bond stretching and types, and other parameters, for building and for electrostatic portions of force field for bonds. analyzing your model. Chem3d Building Atom Types. Building types The parameter tables must be located in the C3D available for building models. Items directory in the same directory as the Conjugated Pisystem Atoms. Bond lengths for Chem3D application. bonds involved in pi systems. Pi system portion of Using Parameter Tables the force field for pi atoms. Conjugated Pisystem Bonds. Pi system portion Chem3D uses several parameter tables to calculate of the force field for pi bonds. bond lengths and bond angles in your model. To apply this information, go to File>Model Set- Electronegativity Adjustments. Adjusts optimal tings>Model Building tab and select the Apply Stan- bond length between two atoms when one atom is dard Measurements checkbox. attached to an atom that is electronegative. Calculating the MM2 force field of a model Elements. Contains elements available for build- requires special parameters for the atoms and ing models. bonds in your model. The MM2 force field is cal- MM2 Atom Type Parameters. van der Waals culated during Energy Minimization, Molecular parameters for computing force field for each Dynamics, and Steric Energy computations. atom. The use of the parameter tables are described MM2 Atom Types. Atom types in the model that below: may be used for MM2 calculations. 3-Membered Ring Angles. Bond angles for MM2 Constants. Constants used for computing bonds in 3-membered rings. In force field analysis, MM2 force field. angle bending portion of the force field for bonds in 3-membered rings. Out-of-Plane Bending Parameters. Parameters to ensure atoms in trigonal planar geometry remain 4-Membered Ring Angles. Bond angles for planar. In force field analysis, parameters to ensure bonds in 4-membered rings. In force field analysis, atoms in trigonal planar geometry remain planar. angle bending portion of the force field for bonds in 4-membered rings. References. Contains information about where parameter information is derived. 4-Membered Ring Torsionals. The portion of the force field for the torsional angles in your Substructures. Contains predrawn substructures model for atoms in 4-membered rings. for fast model building. Angle Bending Parameters. Standard bond Torsional Parameters. Computes the portion of angles. In force field analysis, the angle bending the force field for the torsional angles in your portion of the force field for bonds. model.

Chem & Bio 3D 201 User Guide 4 The parameter is well-confirmed. Creating Parameters Creating on a based are The field parameters force MM2 These atom atom types. of MM2 number limited atom types found in common the types cover As discussed in the previousorganic compounds. Reference The correspondsa measurement reference for a to Refer- table. in the References number reference was parameter data the where ences indicate derived. Estimating Parameters & Bio 3D 11.0 Chem In certain circumstances, estimate parameters. may a assume analysis, an MM2 during example, For non-MM2 model. atom type is encountered in your Atom theinAlthough type is defined the atom the necessarytable, will not MM2 parameter Types tor- example, For be for defined that atom type. This commonly be missing. sional parameters may MM2 does which inorganicoccurs for complexes, Moreexist for parameters adequately. notcover organic compounds. an edu- makes 3D 11.0 & Bio Chem In this case, A messageindi- possible. wherever cated “guess” appear before erroran model may cating in your to ignore this, choose you If start you the analysis. can determineyou the parameters guessed after the analysis is complete. MM2 analysis, used in an view the parameters To go Used toParameters. Calculations>MM2>Show of 1. a Quality value have Estimated parameters . Adjusts specific van specific Adjusts van confirmed. mental data. 202 • Numbers Type Atom •Quality • Reference 3 from experi- Theparameter is derived Quality Accuracy Level 12 The Chem3D. by parameter a guess The parameter is theorized but not Quality The indicates the relative of a parameter quality data. of the accuracy Atom Type Numbers Atom Type The firstparameterin column table references a an An Atom number. atom type usingType an Atom is assigned type in to an atom number the Type a in Chem3D, example, For table. Types Atom Torsional 1–1–1–4, in the dihedral type field, torsionalangle table indicates a Parameters carbon of type alkane (Atom atoms Type between 1) and number carbon atoms of type alkyne (Atom the 4). In the 3-membered ring table, number Type 22-22-22, angle angleindicates an type field, (Atom Type three cyclopropyl carbons between ring cyclopropane 22) in a number Parameter Table Fields Table Parameter ofthe tables contain types of Most the following fields: van der Waals Interactions. Interactions. der Waals van bonding. hydrogen as such interactions, der Waals

Administrator section, parameters may be missing from struc- Four fields comprise a record in the Elements tures containing other than an MM2 atom type. table: the symbol, the covalent radius, the color, and the atomic number. NOTE: Adding or changing parameter tables is not recom- Symbol. Normally you use only the first column mended unless you are sure of the information your are add- of the Elements table while building models. If you ing. For example, new parameter information that is are not currently editing a text cell, you can quickly documented in journals. move from one element to another by typing the first letter or letters of the element symbol.

To add a new parameter to a parameter table: Cov Rad. The covalent radius is used to approximate bond lengths between atoms. 1. Go to View>Parameter Tables and choose the Color. The colors of elements are used when the parameter table to open. Color by Element check box is selected in the con- 2. Right-click a row header and choose Append Row trol panel. To change the color of an element, dou- from the context menu. A blank row is inserted. ble-click the current color. The Color Picker dialog 3. Type the information for the new parameter. box appears in which you can specify a new color 4. Close and Save the file. for the element.

NOTE: Do not include duplicate parameters. If duplicate Building Types parameters exist in a parameter table it is indeterminate The Chem3D Building Atom Types table XML file which parameter will be used when called for in a calculation. (Chem3D Building Atom Types.xml) contains the atom types used in building models.

Normally you use only the first column of the NOTE: If you do want to make changes to any of the Chem3D Building Atom Types table while build- parameters used in Chem3D, it is strongly recommended that ing models. To use a building type in a model, type you make a back up copy of the original parameter table and its name in the Replacement text box (or paste it, remove it from the C3DTABLE directory. after copying the name cell to the Clipboard) and press the Enter key when an atom is selected, or when you double-click an atom. If no atom is The Elements selected, a fragment is added. Twelve fields comprise a building type record: The Elements table (Elements.xml) contains the name, symbol, van der Waals radius, text number, elements for building your models. charge, the maximum ring size, rectification type, To use an element in a model, type its symbol in geometry, number of double bonds, number of tri- the Replacement text box (or paste it, after copying ple bonds, number of delocalized bonds, bound-to the cell in the “Symbol” field to the Clipboard) and order and bound-to type. press the Enter key when an atom is selected, or double-click an atom. If no atom is selected, a frag- Name. The records are ordered alphabetically by ment is added. atom type name. Building type names must be unique.

Chem & Bio 3D 203 User Guide speci- tab, tab, Model Building Model is 3. The rectification type . On . On the check box. The maximum ring size field indicates size field indicates ring Themaximum Thegeometry a building type for Rectify C Cyclopropane •H Alcohol •H Amide •H •D Enol •H Alcohol Ammonium •H •H Amine •H •H Carboxyl •H • H Guanidine • H Thiol Rectification Type. Type. Rectification rectification types are: Possible the bound-to type, a rectification specify When you rectificationthe type of conflict type should not is no rectification If there with the building type. rectified. type for an atom, it is never O Carboxyl of type if the rectification example, For H Carboxyl the bound-to type of Carboxyl, is H Otherwise, or empty. either O Carboxyl be should atoms hydrogen when assigning building types, H notare assigned atoms bound to O Carboxyl Carboxyl. Geometry. bonds that extend of both the number describes from this type of atom and the angles formed by those bonds. fies the type of atom used to fill open valences. open valences. of atom used to fill fies the type Rectification atoms are added or deleted as you deleted as you atoms are added or Rectification rectification,go to activate model. To your build Settings File>Model Chem & Bio 3D displays the formal displays & Bio 3D Chem charge that the and calculates assignedhas been to atoms delo- (when Both charges are displayed calized charge. hover when you applicable) in the popup window an atom. over Max Ring. correspondingwhether the be type should building of a certain to atoms found in rings restricted size. then this building type If this is zero or empty, cell ring maximum the example, is not restricted. For size of select the

) in O Alcohol command (go to when displaying the when displaying atom and an ing types, such as MDL as such ing types, to specify the size of size the specify to The van der Waals (van (van der Waals The van . has a building type num- has a building type number type number building a has Close Contacts C Alkane C Alkane O Alcohol This symbol element the field contains The charge of a building type is used The type building charge of a The van der Waals radii specifiedin the Chem3D der Waals The van and and 1 Text numbers are used to determine are used numbers which Text To determine the standardof a bond length To . 6 204 other parameter tables other parameter atom, look the at 1-6 record in the Bond Stretching table. Charge. in a model. when assigning building types to atoms When the information an atom is displayed, about the charge. by followed the atom symbol is always the charge example, Charges can be fractional. For a carbon atom in a cyclopentadienyl ring is of 0.200. bond between a bond between determines comparing the dis- contacts by close pairs of non-bonded to the atoms tance between radii. der Waals sum of their van atomballs andsurfaces dot of are table. specified in theMM2 Atom Types Text. group of atoms apply to a given measurements NOTE: Structure>Measurements>Generate All CloseContacts MolFile. Radius. Waals der van Symbol. The associated links with the symbol type. building the table and Types Building Atom the Chem3D Theused in is symbol element table. Elements in file formatsfiles save and when you atom labels not supportthat do build radius is used der Waals) ber of For example, BuildingAtom Types table do not affect do not table the resultsBuildingAtom Types of an The radii used in MM2 computations MM2 computation. Ball & Stick, CylindricalBonds or Space Filling Ball& Stick, models. The Generate All

Administrator Possible geometries are: Bound-to Type. Specifies the building type to which the atom must be bound. If there is no •0 Ligand •1 Ligand restriction, this field is empty. The Bound-to type is used in conjunction with the Bound-to Order field. • 5 Ligands • Bent Non-blank Bound-to-Type values: •Linear •Octahedral • C Alkene • C Carbocation • Square planar • Tetrahedral •C Carbonyl •C Carboxylate • Trigonal bipyramidal • Trigonal planar • C Cyclopentadienyl • C Cyclopropene • Trigonal pyramidal • C Epoxy • C Isonitrile

NOTE: Standard bond angle parameters are used only •C Metal CO •C Thiocarbonyl when the central atom has a tetrahedral, trigonal or bent •H Alcohol •H Thiol geometry. • N Ammonium • N Azide Center

Double, Triple, and Delocalized Bonds. The • N Azide End • N Isonitrile number of double bonds, number of triple bonds, •N Nitro •O Carbonyl and number of delocalized bonds are integers ranging from zero to the number of ligands as specified • O Carboxylate • O Epoxy by the geometry. Chem3D uses this information both to assign building types based on the bond •O Metal CO •O Nitro orders and to assign bond orders based on building • O Oxo • O Phosphate types. • P Phosphate • S Thiocarbonyl Bound-to Order. Specifies the order of the bond acceptable between a building type and the atom type specified in the bound-to type. Substructures For example, for C Carbonyl, only double bonds The Substructure table (Substructures.xml) con- can be formed to bound-to type O Carboxylate. If tains substructures to use in your model. there is no bound-to type specified, this field is not To use a substructure simply type its name in the used. The possible bound-to bond orders are sin- Replacement text box (or paste it, after copying the gle, double, triple, and delocalized. name cell to the Clipboard) and press the Enter key when an atom(s) is selected, or double-click an NOTE: The bound-to order should be consistent with the atom. You can also copy the substructures picture number of double, triple, and delocalized bonds for this atom to the Clipboard and paste it into a model window. type. If the bound-to type of an atom type is not specified, its The substructure is attached to selected atom(s) in bound-to order is ignored. the model window. If no atom is selected, a fragment is added. You can also define your own substructures and add them to the table. The table below shows the substructure table window with

Chem & Bio 3D 205 User Guide ted by the second atom the second ted by of the polarity of the of the polarity of Thefield contains the bond Bond Dpl ThethirdLength, field, contains the The 1-5 bond type has a dipole of zero,dipole of despitehas a The 1-5 bond type the The KS, or bond stretching force constant or bond stretching The KS, NOTE: to producefound results. acceptable fact that the carbon and hydrogen atoms on this bond havethis bond atoms on hydrogen the carbon and that fact drasticallyapproximation This unequal electronegativity. reducesdipoles has been to be computed and of the number KS. field, containsproportionality a constantwhich thedirectly strength impacts ofbond between a The largerof KS for a partic- the value atoms. two the more itdifficult atoms, two ular bond between that bond. or to stretch is to compress Length. bond lengtha particular for The bondlarger type. the longer in the Length field, that the number is bond. type of Bond Dpl. in The numbers for a particulardipole type. bond indication an this cell give particular of zero indicates that value bond. A there is no difference in the electronegativity of the atoms in a particular bond dipole bond. A positive that the the building type representedindicates by is field Bond Type the in atomfirst type number than the buildingelectronegative type repre-less a Finally, the second atom type number. by sented dipole means that the building type bond negative in number type building the first represented by than field is more electronegative the Bond Type the building type represen type number. dipole bond the 1-1 bond type has a example, For bothsince zero alkane carbons of in the bond are The 1-6 bond type of the same electronegativity. or alco- of 0.440 since an ether has a bond dipole alkane an than is more electronegative hol oxygen carbon. the 1-19typebondhas a bond dipole Finally, -of electronega- 0.600since a silane silicon is less than an alkane carbon. tive rce field for the bonds in Thedescription reference contains The Bond Type field contains the The Bond Type The reference number is an index by by an index is Thenumber reference 206 Bond Stretching Parameters Bond Stretching (Bond table Parameters TheStretching Bond contains information Parameters.xml) Stretching atoms of about standard bond lengths between In addition to standard atom types. bond various lengths is information used in MM2 calculations in Chem3D. table containsTheparameters Stretching Bond and elec- needed to compute the bond stretching trostatic portionsof the fo your model. record consists of The Parameters Bond Stretching Dpl, Bond Length, KS, Type, Bond fields: six and Reference. Quality, Bond Type. building type numbers of the two bonded atoms. of the two building type numbers an between bond 1-2 is a Bond Type example, For carbon. alkane carbon and an alkene References contains table (References.xml) The References information concerningother for the source does not table of the References Use parameters. way. any in affect the other tables record: the reference used for each are fields Two and the reference description. number reference Number. the substructure facing open (triangles records Therecord. the closes triangle a Clicking down). substructurethe picture of is minimized. organized. are measure- the references Each which a reference field that should ment also contains source the indicating a reference number, contain for that measurement. Description. to describe the reference. want text you whatever bibliographic or references data are com- Journal mon examples.

Administrator Record Order Each of the records in the Angle Bending table, the 4-Membered Ring Angles table and the 3-Mem- The order of the records in the Bond Stretching bered Ring Angles table consists of seven fields, table window is as follows: described below: 1. Records are sorted by the first atom type number Angle Type. The Angle Type field contains the in the Bond Type field. For example, the record atom type numbers of the three atoms that create for bond type 1-3 is before the record for bond the bond angle. type 2-3. For example, angle type 1-2-1 is a bond angle 2. For records where the first atom type number is formed by an alkane carbon bonded to an alkene the same, the records are sorted by the second carbon, which is bonded to another alkane carbon. atom type number in the Bond Type field. For Notice that the alkene carbon is the central atom example, bond type 1-1 is before the record for of the bond angle. bond type 1-2. KB. The KB, or the angle bending constant, con- Angle Bending Parameters tains a measure of the amount of energy required to deform a particular bond angle. The larger the • 4-Membered Ring Angle Bending value of KB for a particular bond angle described • 3-Membered Ring Angle Bending by three atoms, the more difficult it is to compress or stretch that bond angle. The Angle Bending table (Angle Bending Parame- ters.xml) describes bond angles between atoms of –XR2–. –XR2–, the third field, contains the opti- various atom type. In addition to standard bond mal value of a bond angle where the central atom angles is information used in MM2 Calculations in of that bond angle is not bonded to any hydrogen Chem3D. Angle bending parameters are used atoms. In the –XR2– notation, X represents the when the central atom has four or fewer attach- central atom of a bond angle and R represents any ments and the bond angle is not in a three or four non-hydrogen atom bonded to X. membered ring. (In three and four membered For example, the optimal value of the 1-1-3 angle rings, the parameters in the 3-Membered Ring type for 2,2-dichloropropionic acid is the –XR2– Angles.xml and 4-Membered Ring Angles.xml are bond angle of 107.8°, since the central carbon (C- used.) 2) has no attached hydrogen atoms. The Angle Bending table contains the parameters The optimal value of the 1-8-1 angle type for used to determine the bond angles in your model. N,N,N-triethylamine is the –XR2– bond angle of In Chem3D Pro, additional information is used to 107.7°, because the central nitrogen has no compute the angle bending portions of the MM2 attached hydrogen atoms. Notice that the central force field for the bond angles in your model. nitrogen has a trigonal pyramidal geometry, thus The 3- and 4-membered Ring Angles table con- one of the attached non-hydrogen atoms is a lone tains the parameters that are needed to determine pair, the other non-hydrogen atom is a carbon. the bond angles in your model that are part of –XRH–. The –XRH– field contains the optimal either 3- or 4-membered rings. In Chem3D, addi- value of a bond angle where the central atom of tional information is used to compute the angle that bond angle is also bonded to one hydrogen bending portions of the MM2 force field for any atom and one non-hydrogen atom. In the –XRH– bond angles in your model that occur in these notation, X and R are the same as –XR2–, and H rings. represents a hydrogen atom bonded to X.

Chem & Bio 3D 207 User Guide larger the more electroneg- The field Atom type number con- The Ionization field contains the The Repulsion field contains a mea- field TheRepulsion The(Conjugated table Pi Atoms Pisys- The Electron field contains the number The number the Electron field contains each on separate pi atoms, from moving apart. from moving on separateeach pi atoms, theoccupying orbital same on the same pi apart. from moving atom, Theof units the repulsion energy The(eV). are electron volts the more energyrepulsion positive more is the atom. electronegative • The electrons, energy two keep to required • The electrons, energy two keep to required Pi Atoms. Pi Atoms. to used parameters the contains tem Atoms.xml) correct bondand lengths angles for pi atoms in additional information is In Chem3D, model. your portions the pi system used to compute of the model. fieldforce in your for the pi atoms MM2 The comprise six Atoms table Pi records in the Electron, Ionization, Repulsion, fields: AtomType, and Reference. Quality, Atom Type. the rest of the to which number tains the atom type Conjugated Pisystem Atoms record applies. Electron. electrons that a particularof pi atom contributes to the pi system. atom type number carbon, an alkene example, For whereas a 2, contributes 1 electron to the pi system pyrrole nitrogen,contrib- 40, atomtypenumber to the pi system. 2 electrons utes Ionization. amount of energy a pi electron to remove required from an isolated piatom. The unit of the ioniza- energytion (eV). The of magnitude volt electron is energythe ionization is the atom. ative carbon an ionization has an alkene example, For and the more electronegative energy of -11.160 eV, pyrrole nitrogen has an ionization energy of - 13.145 eV. Repulsion. sure of: 07.7°, because the central because the central 07.7°, –XH2– is the optimal value of a bond bond of a optimal value the –XH2– is 208 number in the Angle Type field. For example, example, For field. in the Angle Type number before is the recordangle for type 1-2-1 bond the recordangle fortype 1-3-1. bond the records are sortedsame, the is type number Angle Type in the number atom type the first by record for bond angle the example, field. For type 1-3-2is listed before the record for bond angle type 2-3-2. the records are the same, are type numbers the in sorted third atom type number the by the record for example, field. For Angle Type listed before the record bond angle type 1-1-1 is anglefor type 1-1-2. bond When sorted by angle type, the order of the When the order of sortedangle type, by 4-Mem- the table, records in the Angle Bending bered Ring Angles table and the 3-Membered Ring follows: as Angles table is 1.sorted the second atom type are by Records 2. atom second where the records multiple For 3. atom first two where the records multiple For Record Order N has one attached hydrogen atom. In this case the In this case atom. hydrogen attached one has N for 1-8-1 angle the –XR2– type and –XRH– values exam- the N,N,N-triethylamine are identical. As in non-hydrogen atom is the only attached ple above, a lone pair. –XH2–. atom of that bond angle is where the central angle atoms. hydrogen also bonded to two 1-1-3 angle of the value the optimal example, For type for propionic acid is the –XH2– bond angle (C-2) has two carbon 110.0°, the central since of atoms. hydrogen attached For example, the optimal value of the 1-1-3 angle 1-1-3 angle of the value optimal the example, For –XRH– the fortype acid is 2-chloropropionic carbon (C- central the of 109.9°, sincebond angle The atom. hydrogen optimal attached 2) has one for N,N-diethylamine type 1-8-1 angle of the value 1 of is the –XRH– value

Administrator For example, an alkene carbon has an repulsion Record Order. When sorted for Bond Type, the energy of 11.134 eV, and the more electronegative order of the records in the Conjugated Pisystem pyrrole nitrogen has an repulsion energy of 17.210 Bonds table is as follows: eV. 1. Records are sorted by the first atom type number Pi Bonds in the Bond Type field. For example, the record for bond type 2-2 is listed before the record for The Pi Bonds table (Conjugated PI System bond type 3-4. Bonds.xml) contains parameters used to correct 2. For records where the first atom type number is bond lengths and bond angles for bonds that are the same, the records are sorted by the second part of a pi system. In Chem3D, additional infor- atom type number in the Bond Type field. For mation is used to compute the pi system portions example, the record for bond type 2-2 is listed of the MM2 force field for the pi bonds in a model. before the record for bond type 2-3. There are five fields in records in the Pi Bonds table: Bond Type, dForce, dLength, Quality, and Electronegativity Adjustments Reference. The parameters contained in the Electronegativity Bond Type. The Bond Type field is described by Adjustments table (Electronegativity Adjust- the atom type numbers of the two bonded atoms. ments.xml) are used to adjust the optimal bond For example, bond type 2-2 is a bond between two length between two atoms when one of the atoms alkene carbons. is attached to a third atom, on that is electronegative. dForce. The dForce field contains a constant used to decrease the bond stretching force constant of a For example, the carbon-carbon single bond length particular conjugated double bond. The force con- in ethane is different from that in ethanol. The stant Kx for a bond with a calculated pi bond order MM2 parameter set has only a single parameter for x is: Kx = K2 - (1 - x) * dForce carbon-carbon single bond lengths (1.523Å). The use of electronegativity correction parameters where K2 is the force constant for a non-conju- allows the C-C bond in ethanol to be corrected. gated double bond, taken from the Bond Stretch- The electronegativity parameter used in the Elec- ing table. tronegativity Corrections table is the 1-1-6 angle The higher the value of Kx for the bond between type, where atom type 1 is a C Alkane and atom two pi atoms, the more difficult it is to compress or type 6 is an O Alcohol. The value of this parameter stretch that bond. is -0.009Å. Thus the C-C bond length in ethanol is dLength. The dLength field contains a constant 0.009Å shorter than the standard C-C bond length. used to increase the bond length of any conjugated double bond. The bond length lx for a bond with a MM2 Constants calculated pi bond order x is: The MM2 Constants table (MM2 Constants.xml) lx = l2 + (1 - x) * dLength contains parameters that Chem3D uses to compute the MM2 force field. where l2 is the bond length of a non-conjugated double bond, taken from the Bond Stretching Cubic and Quartic Stretch Constants table. The higher the value of lx for the bond between two pi atoms, the longer that bond is. Integrating the Hooke's Law equation provides the Hooke's Law potential function, which describes

Chem & Bio 3D 209 User Guide mpared to a C-C-C bond mpared to represent any non-hydro- om the aforementioned - 1.550Å, from a C-C bond constant constant • interaction force Stretch-Bend X-B,C,N,O-Y • interaction force Stretch-Bend X-B,C,N,O-H •constant force X-Al,S-Y Stretch-Bend • force X-Al,S-H constant Stretch-Bend • force constant X-Si,P-Y Stretch-Bend • force constant Stretch-Bend X-Si,P-H • force constant Stretch-Bend X-Ga,Ge,As,Se-Y carbons with one or two attached hydrogens differ hydrogens attached with carbons one or two from hydro- for those carbons no attached with attached carbons one or two with Because gens. separate con- force occur, frequently hydrogens angles. bond these for used stants are Theallows K for 1-1-1 angles -CHR- Bending to be specified for force constants more accurate 2 (-CHR-) interac- Type 1 (-CH2-) and the Type for 1-1-1 addition, In Bending K the -CHR- tions. Bend- and the -CHR- rings 4-membered in angles is the atom type (22 angles 22-22-22 K for ing Cyclopropane for the C atom type) in 3- number rings differ fr membered CHR- Bending K for angles and 1-1-1 thus require separatespecified. constants to be accurately Stretch-Bend Parameters Stretch-Bend The are force constants parameters stretch-bend termsinteraction for the stretch-bend in the prior X and Y elements. list of gen atom. field MM2 force Whenthe an angle is compressed, constants to lengthen force the stretch-bend uses angle to the the bonds from the central atom in the atoms in the angle. two other the normal example, C-C-C bond angle in For cyclobutane is 88.0°, as co The in cyclohexane. stretch-bend of 110.8° angle force constants are used to lengthen the C-C bonds in cyclobutane to length of 1.536Å in cyclohexane. 2 kx - 1 -- 2 = dx – x 0 ∫ ° = e balland spring model. Fdx = = Vkx d dx dV ------x 0 – ∫ ° = () Vx membered rings bered rings 210 •3- for 22-22-22 angles in K -CHR- Bending •for 1-1-1 angles K -CHR- Bending • angles in 4-mem- for 1-1-1 K -CHR- Bending These constants are distinct from the force con- Thesethe force are distinct from constants The table. stants specified in the Angle Bending bending force constant (K) for the 1-1-1 angle (1 is for the C Alkane atom type) the atom type number listed in the MM2 Angle Bending parameters table non-hydrogen for an alkanecarbon with two is groupsAngle bending parameters for attached. Type 2 (-CHR-) Bending Force Parameters for Force Bending 2 (-CHR-) Type C-C-C Angles Certain are containwhich long molecules bonds this reason For Law. Hooke's by not described well term. a cubic stretch force field contains the MM2 The term asymmetric cubic stretch an for allows these allowing thereby potential well, the shape of the cubic long bonds to be handled. However, termstretch is not sufficient to handle abnormally Thus a field contains the MM2 force bonds. long quartic term stretch to correctcaused for problems these abnormallyby long bonds. the potential energythe potential th of potential functionThe is quadratic, Law Hooke's The created is symmetrical. well potential the thus is asymmetric and is real shape of the potential well the Morse Function, but the Hooke's by defined for most well mole- potential function Law works cules. The the classical is function of this potential shape potential well.

Administrator Sextic Bending Constant Each MM2 Atom Type record contains eight Sextic bending constant ( 10 8) fields: Atom type number, R*, Eps, Reduct, * ** Atomic Weight, Lone Pairs, Quality, and Reference. Chem3D uses the sextic bending constant to increase the energy of angles with large deforma- Text type number tions from their ideal value. The Text number field is the atom type to which Dielectric Constants the rest of the MM2 Atom Type Parameter record applies. The records in the MM2 Atom Type table • Dielectric constant for charges window are sorted in ascending order of Atom • Dielectric constant for dipoles Type Atom type number. The dielectric constants perform as inverse pro- R portionality constants in the electrostatic energy terms. The constants for the charge and dipole The R field is the van der Waals radius of the par- terms are supplied separately so that either can be ticular atom. The larger the van der Waals radius of partially or completely suppressed. an atom is, the larger that atom. The charge-dipole interaction uses the geometric mean of the charge and dipole dielectric constants. NOTE: Chem3D uses the van der Waals radius, R, in the For example, when you increase the Dielectric con- MM2 Atom Types table for computation. It is not the same stant for dipoles, a decrease in the Dipole/Dipole as the van der Waals radius in the Atom Types table, which energy occurs. This has the effect of reducing the is used for displaying the model. contribution of dipole-dipole interactions to the total steric energy of a molecule. Eps Electrostatic and van der Waals Cutoff The Eps or Epsilon field is a constant that is pro- Parameters portional to the depth of the potential well. As the • Cutoff distance for charge/charge interactions value of epsilon increases, the depth of the poten- Cutoff distance for charge/dipole interactions tial well increases, as does the strength of the repulsive and attractive interactions between an atom • Cutoff distance for dipole/dipole interactions and other atoms. • Cutoff distance for van der Waals interactions

These parameters define the minimum distance at NOTE: For specific van der Waals interactions, the R and which the fifth-order polynomial switching func- Eps values from the van der Waals Interactions table are tion is used for the computation of the listed inter- used instead of values in the MM2 Atom Types table. See actions. “van der Waals Interactions” for more information. MM2 Atom Type Parameters Reduct The MM2 Atom Types table (MM2 Atom Types.xml) contains the van der Waals parameters Reduct is a constant used to position the center of used to compute the force field for each atom in the electron cloud on a hydrogen atom toward the your model. nucleus of the carbon atom to which it is bonded by approximately 10% of the distance between the two atoms.

Chem & Bio 3D 211 User Guide three principal torsional three principal Lone pairs areLone pairs not automatically displayedin Dihedral Type field contains the atom type The Dihedral Type the of the four atom types that describe numbers dihedral angle. dihedral angle angle type 1-2-2-1 is a example, For formed carbon an alkane bonded to an alkene by carbon alkene carbon to a second that is bonded in turn,which, is bonded to another alkane carbon. angle type 1-2-2-1 is the dihedral words, In other groups2-butene. methyl of the two between angle carbons are the centralatoms of alkene The two the dihedralangle. V1 constant, Torsional The V1, or 360° Periodicity field contains the first of torsional used to compute the total constants the its name from energyderives V1 in a molecule. periodicity torsional constant of 360° factthat a only one torsional energy and can have minimum NOTE: requireatoms that them. Parameters Torsional Parame- (Torsional table Parameters The Torsional contains parameters used to compute the ters.xml) portions force field for the torsional of the MM2 model. The Ring Tor- 4-Membered your in angles (4-membered Ring Torsion- sional Parameters contains torsional parameters for atomsals.xml) in 4-membered rings. Parameters of the records in the Torsional Each Parame- table and the 4-Membered Ring Torsional V1, Type, Dihedral fields:six ters table consists of and Reference. V2, V3, Quality, spherical electron distributions, no explicitlone electronsphericaldistributions, are necessary. pairs C. 12 electron cloud centered cloud electron centered The atomic weight the isotopicallyis for pureele- 212 Lone Pairs of lone contains the number field ThePairs Lone Noticethata particularan pairs around atom type. amine nitrogen, 8, has one lone atom type number pair 6, has and atom type number an ether oxygen, Lone pairs are treated explicitly for pairs. lone two distinctly have which as these, atoms such atom For non-sphericaldistributions. electron more nearly have O Carbonyl, which as types such NOTE: 12.000, weight1 is the atomic of Atomic Weight is the atomic The fifthAtomic Weight, field, represented of atoms this atom type weight by number. Any atom in a van der Waals potential function function potential Waals der a van atom in Any a spherical possess must largermost is a atoms this For about its nucleus. such for smaller atoms assumption,reasonable but calcula- Molecular mechanics it is not. hydrogen as clouds centered electron on spherical tions based results. accurate do not give nuclei about hydrogen a reasonable it is compromise to assume However, is still about hydrogen that the electron cloud islongerthat nospherical, it but centered on the multi- constant is The Reduct nucleus. hydrogen the normalby a new plied bond length to give representsthewhich bond length the center of repositioned electron cloud. for all non-hydrogen field of the Reduct The value zero. atoms is ment. For example, the atomic weight atom type number for example, ment. For

Administrator one torsional energy maximum within a 360° sions about carbon-carbon single bonds. A conse- period. The period starts at -180° and ends at 180°. quence of this difference in V2 values is that the A positive value of V1 means that a maximum energy barrier for rotations about double bonds is occurs at 0° and a minimum occurs at ±180° in a much higher than the barrier for rotations about 360° period. A negative value of V1 means that a single bonds. minimum occurs at 0° and a maximum occurs at The V1 torsional constant creates a torsional ±180° in a 360° period. The significance of V1 is energy difference between the conformations rep- explained in the example following the V2 discus- resented by the two torsional energy minima of the sion. V2 constant. As discussed previously, a negative value of V1 means that a torsional energy mini- V2 mum occurs at 0° and a torsional energy maximum The V2, or 180° Periodicity Torsional constant, occurs at 180°. The value of V1=-0.100 means that field contains the second of three principal tor- cis-2-butene is a torsional energy minimum that is sional constants used to compute the total tor- 0.100 kcal/mole lower in energy than the torsional sional energy in a molecule. V2 derives its name energy maximum represented by trans-2-butene. from the fact that a torsional constant of 180° peri- The counterintuitive fact that the V1 field is nega- odicity can have only two torsional energy minima tive can be understood by remembering that only and two torsional energy maxima within a 360° the total energy can be compared to experimental period. results. In fact, the total energy of trans-2-butene is A positive value of V2 indicates there are minima computed to be 1.423 kcal/mole lower than the at 0° and +180°, and there are maxima at -90° and total energy of cis-2-butene. This corresponds +90° in a 360° period. A negative value of V2 closely with experimental results. The negative V1 causes the position of the maxima and minima to term has been introduced to compensate for an be switched, as in the case of V1 above. The signif- overestimation of the energy difference based icance of V2 is explained in the following example. solely on van der Waals repulsion between the A good example of the significance of the V1 and methyl groups and hydrogens on opposite ends of V2 torsional constants exists in the 1-2-2-1 tor- the double bond. This example illustrates an sional parameter of 2-butene. The values of V1 and important lesson: V2 in the Torsional Parameters table are -0.100 and There is not necessarily any correspondence 10.000 respectively. between the value of a particular parameter used in Because a positive value of V2 indicates that there MM2 calculations and value of a particular physical are minima at 0° and +180°, these minima signify property of a molecule. cis-2-butene and trans-2-butene respectively. V3 Notice that V2 for torsional parameters involving torsions about carbon-carbon double bonds all The V3, or 120° Periodicity Torsional constant, have values ranging from approximately V2=8.000 field contains the third of three principal torsional to V2=16.250. In addition, V2 torsional parame- constants used to compute the total torsional ters involving torsions about carbon-carbon single energy in a molecule. V3 derives its name from the bonds all have values ranging from approximately fact that a torsional constant of 120° periodicity V2=-2.000 to V2=0.950. can have three torsional energy minima and three torsional energy maxima within a 360° period. A The values of V2 for torsions about carbon-carbon positive value of V3 indicates there are minima at - double bonds are higher than those values for tor-

Chem & Bio 3D 213 User Guide 5-1-3-1 is listed before listed before the record listed before the record ecords in the Out-of-Plane number in the Dihedral Type field. For example, example, For field. in the Dihedral Type number is listed for dihedral type 1-1-1-1 the record recordbefore the for type dihedral 1-2-1-1. are sortedrecords the third the by is the same, field. Type in the Dihedral atom type number the record for dihedral example, typeFor 1-1-1-1 for dihedral typeis listed before the record 1-1- 2-1. the records are the same, are atom type numbers the in number type sortedatom the first by record the for example, field. For Dihedral Type dihedral type 5-1-3-1 is for dihedral type 6-1-3-1. the the same, are third atom type numbers records are sorted the fourth by atom type num- the example, For field. Dihedral Type ber in the record for dihedral type the record for dihedral type 5-1-3-2. Out-of-Plane Bending The(Out-of-Plane Bending table Out-of-Plane containsparameters that Bending Parameters.xml) ensure that atoms with trigonal planar geometry remain planar in MM2 calculations. Therein r are four fields Con- Force Bond Type, table: Bending Parameters stant, Quality and Reference. Bond Type is described which Thethe Bond Type, first field is bonded of the two the atom type numbers by atoms. an is a bond between 2-3 Type Bond example, For and carbon a carbonylalkene carbon. 4-Membered Ring Torsional Parameters table istable as Parameters 4-Membered Ring Torsional follows: 1. are sorted second the atom type by Records 2. type number the second atom records where For 3.third and where the second records multiple For 4. records where the first, second and multiple For The results of MM2 calculations on hydrocarbons 214 When sorted by Dihedral Angle, the order of the When sortedDihedral Angle, by and the table Parameters records in the Torsional dence to any particular propertydence to physical hydrocarbons. of Record Order NOTE: 60°, +60° and +180° and there are maxima at - at maxima are +180°+60° and and there 60°, A negative period. in a 360° +120° 0°, and 120°, maxima and the position of the of V3 causes value as in the case of V1 V2 and be reversed, minima to The in the explained is V3 significance of above. example. following The 1-1-1-1torsional parameter is an of n-butane example of the V3 constant. Thetorsional values table Parameters Torsional V3 in the V1, V2 and of a Because 0.093 respectively. 0.270 and are 0.200, that there are minima of V3 indicates value positive - +180° and there are maxima at at -60°, +60° and 120°, 0°, and +120°, the minima at ±60° signify conformationsthe two the of n-butane in which groupsmethyl are The gauche to one another. represents+180° minimum the conformation in groupsanother. one are anti to the methyl which at 0° representsThe conformation the maximum groups The are eclipsed. the methyl max- in which ima at ±120° conform a methyl in which n-butane group are eclipsed. a hydrogen and The constants in this example V1 and V2 torsional the to affect the torsional energy way similar in a V1 torsionalfor torsions constant about a carbon- carbon double bond (see previous example). do not correspond well with the experimental data on hydro- is used (when torsional constant V3 only the carbons when V2 areV1 and to zero). set However, including small values for the V1 and V2 torsional constants in the MM2 cal- dramaticallyhydrocarbons culations for improve the correspondenceresults of the MM2 with experimental results. providesV1 and V2 This useof little correspon-

Administrator Force Constant tions in a molecule, such as hydrogen bonding, to The Force Constant field, or the out-of-plane provide better correspondence with experimental bending constant, field contains a measure of the data in calculating the MM2 force field. amount of energy required to cause a trigonal pla- For example, consider the van der Waals interac- nar atom to become non-planar. The larger the tion between an alkane carbon (Atom Type 1) and value of Force Constant for a particular atom, the a hydrogen (Atom Type 5). Normally, the van der more difficult it is to coerce that atom to be non- Waals energy is based on the sum of the van der planar. Waals radii for these atoms, found for each atom in the Atom Types table (1.900Å for Atom type num- Record Order ber 1 + 1.400Å for Atom type number 2 = When sorted by Bond Type, the order of the 3.400Å). However, better correspondence between records in the Out-of-Plane Bending Parameters the computed van der Waals energy and experi- table is as follows: mental data is found by substituting this sum with the value found in the van der Waals Interactions 1. Records are sorted by the first atom type number table for this specific atom type pair (Atom Types in the Bond Type field. For example, the record 1-5 = 3.340Å). Similarly, an Eps parameter is sub- for bond type 2-1 is before the record for bond stituted for the geometric mean of the Eps param- type 3-1. eters for a pair of atoms if their atom types appear 2. For records where the first atom type number is in the van der Waals Interactions table. the same, the records are sorted by the second atom type number in the Bond Type field. For Record Order example, the record for bond type 2-1 is before When sorted by Atom Type, the order of the the record for bond type 2-2. records in van der Waals Interactions table window is as follows: NOTE: Out-of-plane bending parameters are not symmet- Records are sorted by the first atom type number rical. For example, the force constant for a 2-3 bond refers to in the Atom Type field. For example, the record for the plane about the type 2 atom. The force constant for a 3- Atom Type 1-36 is before the record for atom type 2 bond refers to the plane about the type 3 atom. 2-21. For records where the first atom type number is the same, the records are sorted by the second van der Waals Interactions atom type number in the Atom Type field. For example, the record for atom type 2-21 is before The parameters contained in the van der Waals the record for atom type 2-23. parameters table (van der Waals Interaction.xml) are used to adjust specific van der Waals interac-

Chem & Bio 3D 215 User Guide 216

Administrator Appendix G: Computation Concepts

Computational chemistry is a field of research for Figure G.1: Computational Chemistry Methods explaining molecular properties using computers Computational Chemistry Methods when actual laboratory investigation may be inappropriate, impractical, or impossible.

Areas of computational chemistry research include: Molecular Quantum • Molecular modeling. Mechanical Methods Mechanical Methods • Computational methods. • Computer-Aided Molecular Design (CAMD). Semiempirical Ab Initio • Chemical databases. Methods Methods • Organic synthesis design. Chem & Bio 3D 11.0 provides the following meth- Molecular modeling can be thought of as the ren- ods: dering of a 2D or 3D model of a molecule’s structure and properties. Computational methods, on the other hand, calculate the structure and prop- Method erty data necessary to render the model. Within a modeling program such as Chem3D, computa- molecular MM2 Chem3D, Tinker tional methods are referred to as computation mechanics MM3, MM3- Tinker engines, while geometry engines and graphics protein Gaussian engines render the model. AMBER,UFF, Chem3D supports a number of powerful compu- Dreiding tational chemistry methods and extensive visualiza- semi- Extended Chem3D, tion options. empirical Hückel MOPAC, Gaussian Methods Overview other semi- MOPAC, Gaussian empirical meth- Computational chemistry encompasses a variety of ods (AM1, mathematical methods that fall into two broad cat- MINDO/3, egories: PM3, etc.) Molecular mechanics. applies the laws of classi- Ab initio RHF, UHF, Gaussian, cal physics to the atoms in a molecule without MP2, etc. GAMESS explicit consideration of electrons. Quantum mechanics. relies on the Schrödinger • Molecular mechanical methods: MM2 equation to describe a molecule with explicit treat- (directly). MM3 and MM3-protein through the ment of electronic structure. Chem3D Tinker interface. Quantum mechanical methods can be subdivided • Semiempirical Extended Hückel, MINDO/3, into two classes: ab initio and semiempirical. MNDO, MNDO-d, AM1 and PM3 methods

Chem & Bio 3D 217 User Guide b , where N is the 4 Some methods depend Requirements increase rela- Requirements , where N is the number of number is the , where N , where N is the number of N is the number where , 2 to molecular mechanics. A to molecular mechanics. 2 or N 3 The be a limiting of a model can size ab initio : The time required for performing calcula- is limited to tens of atoms, semiempirical to is to tenslimited of atoms, determined some (as required parameters by methods) • The molecule of the and size nature • The type of information sought • of applicable experimentally The availability • resources Computer number of atoms in the model. in the atoms of number Semiempirical: The time required for computation increases as N atoms in the model. MM2: The time required for performing computa- as N increases tions atoms. atoms. In general, methods require molecular mechanical less computer resources than quantum mechanical general Theof each suitability method methods. for particular applicationsas can be summarized follows. The importantmost three criteria are: of the these Model size. factorparticular for a Themethod. limiting num- approxi- molecule increasesber of atoms in a by method magnitude between mately one order of classes from initio to thousands. molecularmechanics and hundreds, Availability. Parameter on experimentally determined parameters to per- atoms contains model the If form computations. parametersthea particular of for which method produce may that method not been derived, have for Molecular mechanics, predictions. invalid force- relies on parameters to define a example, field.to the limited force-field is only applicable A it is parametrized. which for of molecules class Computer resources. of the meth- each model for size of the the to tive ods. Ab initio tions increases on the order of N The energya of tes of a model resulting a model resulting tes of A systematic modifica- Predicts certain physical methods through the Chem3D Gauss- the Chem3D methods through ian or GAMESS interface. interface. ian or GAMESS Ab initio through Chem3D and CS MOPAC or Gauss- MOPAC and CS Chem3D through ian. 218 • Choosing the Best Method for all Not all types of calculations are possible and no onemethods for all pur- method is best method application, each given any For poses. of Thechoice and disadvantages. poses advantages including: dependof factors, method on a number given geometry is given a model, which atomsinthe of atthat point. of the PES the value Geometry optimization. Using Computational Methods Using Computational Computational methods the potential calculate energy The PES is the of molecules. surfaces (PES) forces of interactionembodiment of the among structural and the PES, From a molecule. atoms in information chemical molecule can be about a the surface The in methods differ the way derived. calculated properties and in the molecular is from the energy derived surface. Theperform methods calcula- basic the following tions: energy point Single calculation. the atomic coordina tion of dipole as charge, such properties, chemical and formation.moment, and heat of Computational methods can perform more spe- as conformational such searches functions, cialized and molecular dynamics simulations. in a geometry in atom where the forces the on each 3-dimensional arrangementA of structure is zero. atoms in the model representingenergylocal a geometry (a stable molecular minimum be to found withouta conformational crossing energy barrier). Property calculation.

Administrator Molecular Mechanics Methods Applications • Heat of Formation for evaluating conforma- Summary tional energies. Molecular mechanics in Chem3D apply to: • Partial atomic charges calculated from the molecular orbital coefficients. • Systems containing thousands of atoms. • Electrostatic potential. • Organic, oligonucleotides, peptides, and sac- • Dipole moment. charides. • Transition-state geometries and energies. • Gas phase only (for MM2). • Bond dissociation energies. Useful techniques available using MM2 methods include: Semiempirical methods available in Chem3D with CS MOPAC or Gaussian apply to: • Energy Minimization for locating stable con- Systems containing up to 120 heavy atoms and 300 formations. total atoms. • Single point energy calculations for comparing Organic, organometallics, and small oligomers conformations of the same molecule. (peptide, nucleotide, saccharide). • Searching conformational space by varying one Gas phase or implicit solvent environment. or two dihedral angles. Ground, transition, and excited states. • Studying molecular motion using Molecular Dynamics. Ab initio methods available in Chem3D with Gaus- sian or Jaguar apply to: Quantum Mechanical Methods Applications Summary • Systems containing up to 150 atoms. • Organic, organometallics, and molecular frag- Useful information determined by quantum ments (catalytic components of an enzyme). mechanical methods includes: • Gas or implicit solvent environment. • Molecular orbital energies and coefficients. • Study ground, transition, and excited states (certain methods). Figure G.2Comparison of Methods

Method Type Advantages Disadvantages Best For

Molecular Mechanics Least intensive compu- Particular force field appli- Large systems that consist (Gaussian) tationally. Gaussian is cable only for a limited of thousands of atoms and Gaussian uses classical fast and is useful with class of molecules Systems or processes with physics and relies on limited computer Does not calculate elec- no breaking or forming of force-field with embed- resources. It can be tronic properties bonds used for molecules as ded empirical parameters Requires experimental large as enzymes. data (or data from ab initio) for parameters

Chem & Bio 3D 219 User Guide Medium-sized systems that systems Medium-sized consist of hundredsof systems Also, atoms. transi- electronic involving tions. atomsof only tens of or elec- systems involving tronic transitions. with- Molecules or systems experimental out available data (“new” chemistry). Systems requiring rigorous accuracy. ) ab initio molecule. molecule. •and ground states the same of states Excited Potential Energy Surfaces (PES) Surfaces Potential Energy potential The true representationa model’s of energy surface surface is a multi-dimensional of whose dimensionality increases with the number inde- three has atom Since each atom coordinates. z coordinates), visualizing a (x, y, pendent variables surface for a many-atom model is impossible. can generalizeby this problem you However, as such independent variables, examining any two of an atom, as shown y coordinates the x and below. for parameters Less rigorous ab ini- than tio methods Requires experimental experimental Requires data (or data from Computationally intensive Smallconsist systems that methods Less demanding com- Less demanding than putationally ab initio Capable of calculating transition and states states excited broad Useful for a range of systems Does not dependon experimental data Capable of calculating transition states and states excited

(Gaussian, but different bonding patterns, such as propy- such bondingbut different patterns, cyclopropane lene and position (ethane and chloroethane). position (ethane and and staggeredand formsethane). of constant atomcomposition (ethane, for exam- reaction a chemical where ple) or a system occurs. 220 • Molecules with identical atomic composition • Molecules slightly differenthaving atomic com- •conformations energies for (eclipsed Relative • molecules or ensemble of molecule having A Semiempirical Gaussian) (MOPAC, These phys- use quantum experimentally ics, empirical param- derived and extensive eters, approximation. ab initio GAMESS) These use quantum phys- are rigorous mathe- ics, and use methods, matical no empiricalparameters Method Type Advantages DisadvantagesFor Best Potential energydifferentiate between: can surfaces Potential Potential Energy Surfaces Potential Energy A potential energy surface (PES) can describe: Figure G.2Comparison of Methods G.2Comparison Figure

Administrator Figure G.3: Potential energy surfaces Single Point Energy Calculations Single point energy calculations can be used to calculate properties of specific geometry of a model. The values of these properties depend on where the model lies on the potential surface as follows: • A single point energy calculation at a global minimum provides information about the

Potential Energy Saddle Point model in its most stable conformation.

Local Minimum • A single point calculation at a local minimum Global Minimum provides information about the model in one of many stable conformations. • A single point calculation at a saddle point pro- The main areas of interest on a potential energy vides information about the transition state of surface are the extrema as indicated by the arrows, the model. are as follows: • A single point energy calculation at any other Global minimum. The most stable conforma- point on the potential energy surface provides tion appears at the extremum where the energy is information about that particular geometry, not lowest. A molecule has only one global minimum. a stable conformation or transition state. Local minima. Additional low energy extrema. Single point energy calculations can be performed Minima are regions of the PES where a change in before or after optimizing geometry. geometry in any direction yields a higher energy geometry. NOTE: Do not compare values from different methods. Saddle point. A stationary point between two low Different methods rely on different assumptions about a given energy extrema. A saddle point is defined as a molecule, and the energies differ by an arbitrary offset. point on the potential energy surface at which there is an increase in energy in all directions except one, and for which the slope (first deriva- Geometry Optimization tive) of the surface is zero. Geometry optimization is used to locate a stable conformation of a model, and should be done NOTE: At the energy minimum, the energy is not zero; the before performing additional computations or first derivative (gradient) of the energy with respect to geome- analyses of a model. try is zero. Locating global and local energy minima is typically done by energy minimization. Locating a sad- All the minima on a potential energy surface of a dle point is optimizing to a transition state. molecule represent stable stationery points where The ability of a geometry optimization to converge the forces on each atom sums to zero. The global to a minimum depends on the starting geometry, minimum represents the most stable conforma- the potential energy function used, and the settings tion; the local minima, less stable conformations; for a minimum acceptable gradient between steps and the saddle points represent transition confor- (convergence criteria). mations between minima.

Chem & Bio 3D 221 User Guide tremum of interest, it is If the point issaddle the ex another minimization performed. The new startinggeometry or in either (a), might result (c). to a case where the original one led in (f) the conformational For space of the model. 5: Themore information, Dihe- see “Tutorial on pagedral 34. Driver” small potential energy will allow which barriers to be crossed. After completing the molecular geometries individual can simulation, dynamics more For and analyzed. then be minimized information see Appendix H: “MM2” • The geometry and can be altered slightly • search to can be employed The Dihedral Driver • can be run,simulation molecular dynamics A geometrya local minimum.Theprox- is (f), which particularnot a but minimum, to a minimum, imity gradi- specifying a minimum can be controlledby Geometry be reached. ent that should (f), rather geometrythan decreasing by (e), can be reached of the gradientthe value the calculation where ends. (energy criterion if a convergence gradi- In theory, minimization can a first-derivative ent) is too lax, result in a geometrypoint. that is near a saddle energy of the value Thisthe gradi- occurs because very is minimum, point, as near a ent near a saddle of at point (c), the derivative example, small. For the energy the minimizer is con- as far as is 0, and Firstcerned, derivative minimum. (c) is a point minimizers cannot, as a rule, cross saddle points to another minimum. reach NOTE: State command. steps to ensure that a the following take can You hasminimization not resulted in a saddle point. best to use a procedurespecifically that locatesa transition such asstate, the CS Pro Transition Optimize To MOPAC rivative energyof the rivative 222 (depending with respect to the on the method) atomic coordinates determines largein how and of geometry increment what direction the next change should be. are again determinedenergyand and derivatives is until convergence continues the process minimization point the at which pro- achieved, terminates.cess on the starting geometry. on the startinggeometry. energychanged single point and another calculation is performeddetermine to the energy of that new conformation. The startinggeometry determinesof the model starting example, For is reached. minimum which at (b), minimization results in geometry (a), which is the globalStarting minimum. at (d) leads to 4. The change is made. 5. energy the the incremental change, Following some conceptsThe illustration shows of following a sin- this plot shows simplicity, For minimization. dimen- plottedgle independent in two variable sions. Geometry optimizations are iterative and begin at begin and Geometryoptimizations iterative are starting some geometry follows: as 1. The single point energycalculation is performed 2. The coordinates of atoms are for some subset 3. Thede first or second

Administrator You can calculate the following properties with the rium values) that describe the interactions computational methods available through between sets of atoms. Chem3D using the PES: • The sum of the interactions determines the • Steric energy conformation of the molecule. •Heat of formation • Molecular mechanical energies have no meaning as absolute quantities. They can only be used to com- • Dipole moment pare relative steric energy (strain) between two • Charge density or more conformations of the same molecule. • COSMO solvation in water The Force-Field • Electrostatic potential • Electron spin density Since molecular mechanics treats bonds as springs, the mathematics of spring deformation (Hooke’s • Hyperfine coupling constants Law) is used to describe the ability of bonds to •Atomic charges stretch, bend, and twist. Non-bonded atoms • Polarizability (greater than two bonds apart) interact through van • Others, such as IR vibrational frequencies der Waals attraction, steric repulsion, and electrostatic attraction and repulsion. These properties are Molecular Mechanics Theory easiest to describe mathematically when atoms are considered as spheres of characteristic radii. Molecular mechanics computes the energy of a The total potential energy, E, of a molecule can be molecule in terms of a set of classical potential described by the following summation of interac- energy functions. The potential energy functions tions: and the parameters used for their evaluation are known as a “force-field”. E= Stretching Energy + Bending Energy + Torsion Energy + Non-bonded Interaction Energy Molecular mechanical methods are based on the following principles: The first three terms are the so-called bonded interactions. In general, these bonded interactions • Nuclei and electrons are lumped together and can be viewed as a strain energy imposed by a treated as unified particles (atoms). model moving from some ideal zero strain confor- • Atoms are typically treated as spheres. mation. The last term, which represents the non- • Bonds are typically treated as springs. bonded interactions, includes the two interactions shown below. • Non-bonded interactions between atoms are described using potential functions derived The total potential energy can be described by the from classical mechanics. following relationships between atoms. The numbers refer to the atom positions in the figure below. • Individual potential functions are used to describe the different interactions: bond 1. Bond Stretching: (1-2) bond stretching between stretching, angle bending, torsion (bond twist- directly bonded atoms ing), and through-space (non-bonded) interac- 2. Angle Bending: (1-3) angle bending between two tions. atoms that are adjacent to a third atom. • Potential energy functions rely on empirically 3. Torsion Energy: (1-4) torsional angle rotation derived parameters (force constants, equilib- between atoms that form a dihedral angle.

Chem & Bio 3D 223 User Guide ab 2 ) o r − . (r

s parameters are assigned to each parameters are assigned to each o ∑ Bonds defines its defines equilibrium length (the o and r 71.94 K s Editing of MM2 parameters should onlydone be = parameter controls the stiffness of the the stiffness parameter controls s data), to 1, where the data is guessed by by guessed where the data is data), to 1, terms switching polynomial order with 5th function sary View>Parameter Tables View>Parameter Stretch • der Waals for Cutoffs electrostaticvan and •neces- when calculations system pi Automatic • and non-bondedconstraints. Torsional E Each parameter is classified by a Quality number. number. Quality a by parameter is classified Each the data. reliability of the indicates This number The quality ranges from 4, where the data is completely from experimental data (or derived initio Chem3D. contains The MM2 Constants, parameter table, parameters that correctadjustable for failings of the potentialin functions outlying situations. NOTE: effects.for its Energy Bond Stretching The energy bond stretching based equation is on law: Hooke's K The force con- (bondstretching stretching spring’s stant), while r standard measurement used in building models). standard measurement used in building Unique K pair ofonpair bonded their atom types based atoms O-C). The C-H, in the parameters are stored (C-C, The constant,table. parameter Stretching Bond with the greatestwith Within by expert of caution users. a force- field equation, parameters operate interdependently; changing one normally requires that others be to changed compensate Chem3D stores the parameters for the potential parameters Chem3D stores the go tables, view these To energy in tables. function to 224 attraction long range at forces dispersion from interaction). der Waals (van (electrostatic interactions). • charge-dipole A interaction term • quartic A term stretching Chem3D uses a modified version of Allinger’s of Allinger’s Chem3D uses a modified version references additional MM2 force field. For MM2 “MM2” Appendix H: see MM2 force TheAllinger’s principal additions to field are: MM2 Different kinds of force-fields have been devel- have Different kinds of force-fields oped. Some include additional energy terms that ofotherdescribe deformations, as the kinds such in adja- and stretching bending between coupling the the accuracy of improve to in order cent bonds, model. mechanical force- The reliability of a molecular mechanical field depends on the parametersand potential the energydescribe the total energyto used functions be optimizeda for must a model. Parameters of particularof potential set energyand functions, fields. not transferable to other force are thus

4. close and are too atoms that for Repulsion 5.quadrupoles dipoles, charges, from Interactions the major interac- shows illustration The following tions.

Administrator 71.94, is a conversion factor to obtain the final The constant, 0.02191418, is a conversion factor to units as kcal/mole. obtain the final units as kcal/mole. The result of this equation is the energy contribu- Unique parameters for angle bending are assigned tion associated with the deformation of the bond to each bonded triplet of atoms based on their from its equilibrium bond length. atom types (C-C-C, C-O-C, C-C-H). For each trip- This simple parabolic model fails when bonds are let of atoms, the equilibrium angle differs depend- stretched toward the point of dissociation. The ing on what other atoms the central atom is Morse function would be the best correction for bonded to. For each angle there are three possibili- this problem. However, the Morse Function leads ties: XR2, XRH or XH2. For example, the XH2 to a large increase in computation time. As an alter- parameter would be used for a C-C-C angle in pro- native, cubic stretch and quartic stretch constants pane, because the other atoms the central atom is are added to provide a result approaching a Morse- bonded to are both hydrogens. For isobutane, the function correction. XRH parameter would be used, and for 2,2-dime- thylpropane, the XR2 parameter would be used. The cubic stretch term allows for an asymmetric shape of the potential well, allowing these long The effect of the Kb and θ0 parameters is to bonds to be handled. However, the cubic stretch broaden or steepen the slope of the parabola. The term is not sufficient to handle abnormally long larger the value of Kb, the more energy is required bonds. A quartic stretch term is used to correct to deform an angle from its equilibrium value. problems caused by these very long bonds. With Shallow potentials are achieved with Kb values less the addition of the cubic and quartic stretch term, than 1.0. the equation for bond stretching becomes: A sextic term is added to increase the energy of angles with large deformations from their ideal 2 3 4 E = 71.94 K [(r − r ) + CS(r − r ) + QS(r − r ) ] value. The sextic bending constant, SF, is defined Stretch ∑ s o o o Bonds in the MM2 Constants table. With the addition of Both the cubic and quartic stretch constants are the sextic term, the equation for angle bending defined in the MM2 Constants table. becomes: To precisely reproduce the energies obtained with 2 6 E = 0.02191418 K [(θ −θ ) + SF(θ −θ ) ] Allinger’s force field: set the cubic and quartic Bend ∑ b o o stretching constant to “0” in the MM2 Constants Angles tables. NOTE: The default value of the sextic force constant is Angle Bending Energy 0.00000007. To precisely reproduce the energies obtained 2 .i.AngleE = 0.02191418bending energy;K (θ − θ ) with Allinger’s force field, set the sextic bending constant to Bend ∑ b o Angles “0” in the MM2 Constants tables. The bending energy equation is also based on Hooke’s law. The Kb parameter controls the stiff- There are three parameter tables for the angle ness of the spring’s bending (angular force con- bending parameters: stant), while θ defines the equilibrium angle. This 0 • Angle Bending parameters equation estimates the energy associated with deformation about the equilibrium bond angle. • 3-Membered Ring Angle Bending parameters • 4-Membered Ring Angle Bending parameters

Chem & Bio 3D 225 User Guide ) -6 R 2.25 - -2 12.5/R − R e ε j ∑ i 290000 ∑ ( ε j ): 6 —the van der Waals radii for the der Waals —the van ∑ —determines depth the the of * j i ε) ∑ 336.176 j * = = R ij + r * i * and R * and —which is the actual distance between the between the actual distance is —which i R ij R atoms atoms Epsilon ( attractive potential energy easy it how and attractive well togetheris to push atoms r = van der Waals van der Waals • • • E where R E At short distances the above equation favors repul- favors equation At shortabove the distances compensate To interactions. dispersive over sive for this at shortterm distances (R=3.311)this is replaced with: The parameters include: Non-Bonded Energy Non-Bonded Thenon-bonded energy represents the pairwise interacting of all possible of the energies sum non-bonded within atoms a predetermined “cut-off ” distance. The non-bonded energy for accounts repulsive dis- at close atoms between experienced forces at longerfelt forces for the attractive and tances, as their rapid falloff It also accounts for distances. farther apartfew a move the interacting atoms by Angstroms. Energy van der Waals forces the distance dominate when Repulsive the than less interacting atoms becomes between sum of their contact radii. In Chem3D repulsion is combines an expo- which an equation modeled by dispersion repulsionnential with an attractive interaction (1/R φ cos3 + 1 allows allows () 1 3 for 22-22- for 2 V b + φ ns refer to the shifts the entire the shifts ) φ cos2 φ n + − 1 () φ 2 2 V for 1-1-1 angles for 1-1-1 for 1-1-1 angles in 4-mem- for 1-1-1 b + b cos(n φ the angle definitio + 1 cos [] + n 2 1 V () 1 2 V column in the Atom Types Table. 1 refers to 1 refers Table. in the Atom Types column ∑ Torsions ∑ /2 parameter is the torsionalthe/2 parameter force con- is Text C-alkane, and 22 refers to C-cyclopropane. to 22 refers and C-alkane, Torsions = n signifies its periodicity. signifies its periodicity. = n 1. The numbers in 226 Twist Twist • parameters Torsional • 4-Membered ring torsions • 3-Membered ring torsions. Ε Ε 22 angles in 3-membered rings require separaterings require 22 angles in 3-membered for accurate specification. constants stant. It determines of the curve. the amplitude The The V The Thecurve parameters about the rotation angle axis. are determined through curve-fitting techniques. torsional rotation are Unique parameters for bonded quartetassigned to each of atoms based on H-C-C-H). C-O-C-N, their atom types (C-C-C-C, three torsional 11.0 provides Chem & Bio 3D parameters tables: This termdihedral for the tendency for accounts an energyangles (torsionals) to have minimum occurringintervals specific at of 360/n. In Chem 11.0,& Bio 3D n can equal2,1, or 3. Torsion Energy Torsion There con- force angle bending additional three are Thesein Constantsthe MM2 table. available stants for specifically constants, are the “-CHR-Bending” hydrogens. attached or two with one carbons TheK -CHR- Bending rings K Bending and the -CHR-bered more accurate force constants to be specified for to be specified constants force more accurate 2 (-CHR-) interactions. Type (-CHR-) and 1 Type The K -CHR-Bending

Administrator The R* and Epsilon parameters are stored in the interaction by the environment (solvent or the MM2 Atom Types table. molecule itself). q q For certain interactions, values in the van der Waals i j E Electrostatic = ∑∑ interactions parameter table are used instead of i j Drij those in the MM2 atom types table. These situa- In Chem3D, the electrostatic energy is modeled tions include interactions where one of the atoms using atomic charges for charged molecules and is very electronegative relative to the other, such as bond dipoles for neutral molecules. in the case of a water molecule. There are three possible interactions accounted for Cutoff Parameters for van der Waals by Chem3D: Interactions •charge/charge The use of cutoff distances for van der Waals • dipole/dipole terms greatly improves the computational speed • dipole/charge for large molecules by eliminating long range, relatively insignificant, interactions from the computa- Each type of interaction uses a different form of tion. the electrostatic equation as shown below: q q Chem3D uses a fifth-order polynomial switching E = 332.05382∑∑ i j function so that the resulting force field maintains i j Dq rij second-order continuity. The cutoff is imple- where the value 332.05382 converts the result to mented gradually, beginning at 90% of the speci- units of kcal/mole. fied cutoff distance. This distance is set in the MM2 Constants table. dipole/dipole contribution The van der Waals interactions fall off as 1/r6, and μi μ j can be cut off at much shorter distances, for exam- E = 14.388 ()cos χ − 3cosα i cosα j ∑∑ D r 3 ple 10Å. This cut off speeds the computations sig- i j μ ij nificantly, even for relatively small molecules. where the value 14.388 converts the result from ergs/mole to kcal/mole, χ is the angle between the two dipoles μ and μ , α and α are the angles the NOTE: To precisely reproduce the energies obtained with i j i j dipoles form with the vector, r , connecting the Allinger’s force field: set the van der Waals cutoff constants ij two at their midpoints, and D is the (effective) to large values in the MM2 Constants table. μ dielectric constant. dipole/charge contribution Electrostatic Energy q μ E = 69.120 i j cosα The electrostatic energy is a function of the charge ∑ ∑ 2 ( j ) i j r D D on the non-bonded atoms, q, their interatomic dis- ij μ q tance, rij, and a molecular dielectric expression, D, where the value 69.120 converts the result to units that accounts for the attenuation of electrostatic of kcal/mole. Bond dipole parameters, μ, for each atom pair are stored in the bond stretching parameter table. The charge, q, is stored in the atom types table. The molecular dielectric expression is set to a constant

Chem & Bio 3D 227 User Guide is

ο θ θ ] 6 ) o θ − θ C θ SF( ion, MM2 may calculate MM2 may ion, s, standard bond lengthsand s, value used is angle of devi- value + θ 2 o θ x − D y θ θ () [ b B K The method used is that of D.H. Lo and M.A. that of D.H. The method used is Plane

of ∑

Out A Ε= ation from coplanarityfrom pair and for an atom ation MM2 uses the following to describe equation uses the OOP MM2 following bending: The formangle same as for the of the equation is the bending, however, set to zero. The illustration below shows the The shows illustration below set to zero. determined pairs atom DB. for The special force constants for each atom pair are The for each special force constants parameters Plane bending located in the Out of Thesextic correction table. used as previously is The sextic constant, described for Angle Bending. in the MM2 Constants table. is located SF, Pi Bonds and Atoms with Pi Bonds MM2 performscontaining models pi systems, For pi orbital SCF computation a Pariser-Parr-Pople defined as a system is pi system. A for each which atomssequence of three or more of types in appear the Conjugate Atoms table. Pi system Because of this computat bondthan orders otherand 2, 1, 1.5, so on. NOTE: twofoldbarriers. torsional Figure G.4: Determination of G.4: Figure Whitehead, Can. J. Chem., 46, 2027(1968),Chem., 46, with hetero-Whitehead,Can. J. Zeisscycle and M.A. White- parameter according to G.D. Chem. Soc. (A), 1727 (1971). The SCF head, J. are bond orders which yields used to scale thecomputation stretchingbond force constant and can be 3 , 1/r 2 uity in the force-field. ger’s force field: set the ger’s of-plane (OOP) bending. bending. of-plane (OOP) hybridization, require an additional hybridization, 2 Chem & Bio 3D 11.0 Bio 3D & use does not a distance- Chem 228 term to account for out- cutoff at much shorter distances, for example 25 shortermuch distances, cutoff at precisely reproduce the To 18Å respectively. and energies obtained with Allin (99, for example) in to largecutoff constants values the MM2 Constants table. OOP Bending arrangedAtoms thatare in a trigonal planar fash- as in sp ion, Thedistances for electrostatic terms,of cutoff use the terms, greatly improves Waals der for van as speed for largecomputational elimi- molecules by nating long-rangefrom the computa- interactions tion. Chem3D uses calculations, der Waals As in the van to functiona fifth-order polynomial switching contin maintain second-order NOTE: dependent dielectric. Electrostatic for Parameters Cutoff Interactions val- as minimum The function is invoked switching or charge/dipole, ues for charge/charge, Thesedipole/dipole interactions are reached. cut- Constants are located in the MM2 off values parameter table. Since the charge-charge interaction energy between point chargesis pro- separatedr a distance by two be the charge-chargeportional must cutoff to 1/r, large,rather depending typically 30 to 40Å, theon dipole- The charge-dipole, size of the molecule. dipole interactionsas 1/r fall off value between 1.0 and 5.0 in the MM2 Atom types types and MM2 Atom 5.0 in the 1.0 between value table.

Administrator The following is a step-wise overview of the pro- •X-Al, S-Y cess: •X-Al, S-H 1. A Fock matrix is generated based on the •X-Si, P-Y favorability of electron sharing between pairs of •X-Si, P-H atoms in a pi system. • X-Ga, Ge, As, Se-Y, P-Y 2. The pi molecular orbitals are computed from the Fock matrix. where X and Y are any non-hydrogen atom. 3. The pi molecular orbitals are used to compute a User-Imposed Constraints new Fock matrix, then this new Fock matrix is used to compute better pi molecular orbitals. Additional terms are included in the force field when constraints are applied to torsional angles Step 2 and 3 are repeated until the computation of and non-bonded distances by the Optimal field in the Fock matrix and the pi molecular orbitals con- the Measurement table. These terms use a har- verge. This method is called the self-consistent monic potential function, where the force constant field technique or a pi-SCF calculation. has been set to a large value (4 for torsional con- 4. A pi bond order is computed from the pi molec- straints and 106 for non-bonded distances) in order ular orbitals. to enforce the constraint. 5. The pi bond order is used to modify the bond For torsional constraints the additional term and length(BLres) and force constant (Ksres) for each force constant is described by: bond in the pi system. Ε= 4(θ − θ ) 2 6. The modified values of K and BL are used ∑ o sres res Torsions in the molecular mechanics portion of the MM2 For non-bonded distance constraints the additional computation to further refine the molecule. term and force constant is:

. Stretch-Bend Cross Terms 6 2 Ε= ∑10 (r − ro ) Stretch-bend cross terms are used when a coupling Distance occurs between bond stretching and angle bending. Molecular Dynamics Simulation For example, when an angle is compressed, the MM2 force field uses the stretch-bend force con- Molecular dynamics simulates molecular motion. stants to lengthen the bonds from the central atom This simulation is useful because motion is inher- in the angle to the other two atoms in the angle. ent to all chemical processes: vibrations, like bond stretching and angle bending, give rise to IR spec- 1 Ε= ∑ K sb()r − ro ()θ − θo tra; chemical reactions, hormone-receptor bind- Stretch / Bend 2 ing, and other complex processes are associated The force constant (Ksb) differs for different atom with many kinds of intramolecular and intermolec- combinations. ular motions. The seven different atom combinations where The MM2 method of molecular dynamics simula- force constants are available for describing the situ- tion uses Newton’s equations of motion to simu- ation follow: late the movement of atoms. •X-B, C, N, O-Y Conformational transitions and local vibrations are the usual subjects of molecular dynamics studies. •B-B, C, N, O-H

Chem & Bio 3D 229 User Guide

i 8 ⁄ t veryold i i old i a m i a ⁄ a – i = = g old i – l and imposes spin restric- and imposes spin l () old 6a i = a + i i veryold i a a 3a ()Δ () + i v = i v is the mass of the atom): is the mass RHF that the method assumes The default Hartree-Fock shel a closed molecule is matrix the Fock The spin restrictions allow tions. (spinSince alphato be simplified. and up) beta paired, the basic electrons are always (spin down) electron closed is restricted to even RHF method shell systems. Further are made to approximations the RHF is presented.anmethod when open shell system has been termedThis approximation the 1/2 elec- In this method, Dewar. tronby approximation electrons 1/2 as two electrons are treated unpaired Thisequal charge the and opposite spin. of allows computation to be performedshell.a closed A as to correct CI calculation is automatically invoked errors in energy inherent to the 1/2 electron values more information For approximation. see “Config- Interaction” on pageuration 231. Methods Available in CS MOPAC Methods Available open shell and methods include both CS MOPAC Config- approximations. shell Hartree-Fock closed either iter- by be estimated may interaction uration multi-electron (SCF) or self-consistent field ative you semi-empirical methods, For (MECI) methods. Hamiltonian approxima- five between choose may tions. New accelerations and velocities are computed at at are computed velocities and accelerations New formulas stepthe following to according each (m , i 8 ⁄ sec- is the is -15 2 old i t is the time t is t Δ () old i a – i freedom in a stepwisefreedom improved coefficients improved ()Δ () t5a is the acceleration, a i Δ i v ++ i x menu can be used to compute a molec- can be used to compute menu ) are then computed with respect to the ) are then computed with respect to the i = are the Cartesian coordinates of the atom, i i x 230 is the velocity, a is the velocity, , and z , and i i acceleration in the previous step, and and acceleration in the previous step, current the stepbetween and the previous step. of potentialThe potential energyderivatives and energy (g Similarly, each atom is moved for y and z, where x atom is moved each Similarly, (B. R. Brooks) is used to compute new positions R. Brooks) is used to compute new (B. step. at each atom of each velocities and following according to the (i)is moved atom Each formula: onds). Thealgorithm Beeman for integrating the equations of motion, with v Molecular Dynamics Formulas Molecular Dynamics Theof a computation consists molecular dynamics interval, series of steps typi- that occur at a fixed x 10 1.0 cally about 2.0 fs (femtoseconds, Calculations Molecular dynamics alters the values of the of the the values alters dynamics Molecular degreesintramolecular of fashion. The steps simula- in a molecular dynamics tion represent the changes position in atom over energy. amount of kinetic a given for time, The in the command (MM2) Dynamics Molecular ular dynamics trajectorya molecule or frag- for of molecular A common use ment in Chem3D. conformationalthe is to explore dynamics space and to prepare sequences molecule, accessible to a of frames representing a molecule in motion. For more information see on Molecular Dynamics Field Calculations”. 8: “Force Chapter new Cartesian coordinates. new Cartesian coordinates. y

Administrator With the addition of the 1/2 electron approxima- For a particular molecule, configuration interaction tion, RHF methods can be run on any starting uses these occupied orbitals as a reference electron configuration. configuration, then promotes the electrons to unoccupied (virtual) orbitals. These new states, UHF Slater determinants or microstates in MOPAC, are The UHF method treats alpha (spin up) and beta then linearly combined with the ground state con- (spin down) electrons separately, allowing them to figuration. The linear combination of microstates occupy different molecular orbitals and thus have yields an improved electronic configuration and different orbital energies. For many open and hence a better representation of the molecule. closed shell systems, this treatment of electrons results in better estimates of the energy in systems Approximate Hamiltonians in where energy levels are closely spaced, and where MOPAC bond breaking is occurring. UHF can be run on both open and closed shell There are five approximation methods available in systems. The major caveat to this method is the MOPAC: time involved. Since alpha and beta electrons are •MINDO/3 treated separately, twice as many integrals need to • MNDO be solved. As your models get large, the time for the computation may make it a less satisfactory •AM1 method. •PM3 Configuration Interaction Ultra • MNDO-d only The effects of electron-electron repulsion are The potential energy functions modify the HF underestimated by SCF-RHF methods, which equations by approximating and parameterizing results in the overestimation of energies. aspects of the Fock matrix. SCF-RHF calculations use a single determinant The approximations in semiempirical MOPAC that includes only the electron configuration that methods play a role in the following areas of the describes the occupied orbitals for most molecules Fock operator: in their ground state. Further, each electron is • The basis set used in constructing the 1-elec- assumed to exist in the average field created by all tron atom orbitals is a minimum basis set of other electrons in the system, which tends to over- only the s and p Slater Type Orbitals (STOs) estimate the repulsion between electrons. Repul- for valence electrons. sive interactions can be minimized by allowing the electrons to exist in more places (i.e. more orbitals, • The core electrons are not explicitly treated. specifically termed virtual orbitals). The multi-elec- Instead they are added to the nucleus. The tron configuration interaction (MECI) method in nuclear charge is termed Neffective. For exam- MOPAC addresses this problem by allowing multiple, carbon has a nuclear charge of +6-2 core ple sets of electron assignments (i.e., configura- electrons for an effective nuclear charge of +4. tions) to be used in constructing the molecular • Many of the 2-electron Coulomb and Exchange wave functions. Molecular wave functions repre- integrals are parameterized based on element. senting different configurations are combined in a manner analogous to the LCAO approach.

Chem & Bio 3D 231 User Guide for example, neopentane. neopentane. for example, cubane. ple, non- repulsive Overly dimer. water example, and bonding hydrogens between interactions other atoms are predicted. In particular, simple H-bonds are generallyto not predicted exist using MNDO. • unstable, are too molecules Sterically crowded • for exam- rings are too stable, Four-membered • Hydrogenvirtuallyare bonds non-existent, for MNDO Applicability and Limitations and MNDO Applicability applied to the shaded elements in be MNDO may the table below: limitationsThe apply to MNDO: following row and column. Parameters dubious of quality are column. Parameters and row (x). by indicated me sulfur compounds are render it inappropriate being for the model studied? in the model? 232 • limitations which have Does the approximation • for the elements method parameterized the Is For more detailed information see the MOPAC more detailed informationFor see the MOPAC online manual. MINDO/3 (Modified Intermediate Neglect of revision 3) is Diatomic Overlap the oldest method. (IntermediateINDO an it is Using diatomic pairs, the where Orbitals) method, Diatomic Neglect of degree than is more theof approximation severe PM3 and AM1. This methods MNDO, NDDO is generallymethod regarded to be of historical although so interest only, method. still more accurately analyzed using this thethat diatomic pairs The table shows following An x indicates are parameterized in MINDO/3. for the the pair indicated by parameter availability MINDO/3 Applicability and Limitations MINDO/3 Applicability and Overall, these potential energy potential these be Overall, may functions progression as a chronological viewed of improve- the to method, MINDO/3 oldest the ments from although the method,However, PM3. newest to designed method were in each improvements found been they have global improvements, make certainto be limited in situations. major questions consider toThe choos- when two ing a potential function are: Choosing a Hamiltonian a Choosing

Administrator • Hypervalent compounds are too unstable, for • In general, errors in ΔHf obtained using example, sulfuric acid. AM1 are about 40% less than those given by • Activation barriers are generally too high. MNDO. • Non-classical structures are predicted to be • AM1 phosphorus has a spurious and very unstable relative to the classical structure, for sharp potential barrier at 3.0Å. The effect of example, ethyl radical. this is to distort otherwise symmetric geom- • Oxygenated substituents on aromatic rings are etries and to introduce spurious activation out-of-plane, for example, nitrobenzene. barriers. A good example is given by P4O6, • The peroxide bond is systematically too short in which the nominally equivalent P-P bonds by about 0.17 Å. are predicted by AM1 to differ by 0.4Å. This is by far the most severe limitation of AM1. • The C-O-C angle in ethers is too large. • Alkyl groups have a systematic error due to AM1 Applicability and Limitations the heat of formation of the CH2 fragment AM1 may be applied to the shaded elements in the being too negative by about 2 kcal/mol. table below: • Nitro compounds, although considerably improved, are still systematically too positive in energy. • The peroxide bond is still systematically too short by about 0.17Å. PM3 Applicability and Limitations PM3 (Parameterized Model revision 3) may be applied to the shaded elements in the following table: Important factors relevant to AM1 are: • AM1 is similar to MNDO; however, there are changes in the core-core repulsion terms and reparameterization. • AM1 is a distinct improvement over MNDO, in that the overall accuracy is considerably improved. Specific improvements are: • The strength of the hydrogen bond in the water dimer is 5.5 kcal/mol, in accordance The following apply to PM3: with experiment. • Activation barriers for reaction are markedly • PM3 is a reparameterization of AM1. better than those of MNDO. • PM3 is a distinct improvement over AM1. • Hypervalent phosphorus compounds are • Hypervalent compounds are predicted with considerably improved relative to MNDO. considerably improved accuracy. • Overall errors in ΔHf are reduced by about 40% relative to AM1.

Chem & Bio 3D 233 User Guide solvation model for solvation) reaction field •Model) Screening (Conductor-like COSMO • (polarizability calculation) POLAR • Function) GREENF (Green’s • self-consistent (Miertus-Scirocco-Tomasi TOM Results obtained from areMNDO-d generallyResults The superior to those obtained from MNDO. neces- is where it used be should MNDO method saryor repeat to compare calculations previously performed MNDO. using indicated by as types of calculations, The following incompatible with are keywords, MOPAC MNDO-d: , this can be corrected, this can be and Limitations by the the use of by The MMOK option. the MMOK For CS MOPAC. in default used by option is more information about MMOK see the online Manual. MOPAC cally non-existent. In part tions of PM3. This of PM3. tions correctedbe should natu- rally as results are of PM3 calculations reported. 234 • The barrierformamidein rotation to is practi- • information Little exists regardinglimita- the MNDO-d Applicability reformulationMNDO-d is a an with of MNDO This include d-orbitals. to extended basis set in be applied to the elements shaded may method the table below.

Administrator Ultra only Appendix H: MM2

This section provides additional information about Other Parameters the MM2 parameters and force field that has not be covered in other areas of the Chem & Bio 3D The rest of the parameters consist of atom types 11.0 documentation. and elements in the periodic table which were not included in the original MM2 force field, such as MM2 Parameters metals. The rectification type of all the non-MM2 atom types in the Chem3D Parameter tables is The original MM2 parameters include the elements Hydrogen (H). The atom type numbers for these commonly used in organic compounds: carbon, atom types range from 111 to 851. The atom type hydrogen, nitrogen, oxygen, sulfur, and halogens. number for each of the non-MM2 atom types in The atom type numbers for these atom types range the MM2 Atom Type Parameters table is based on from 1 to 50. the atomic number of the element and the number The MM2 parameters were derived from three of ligands in the geometry for that atom type. To sources: determine an atom type number, the atomic num- • Most of the parameters were provided by ber is multiplied by ten, and the number of ligands Dr. N. L. Allinger. is added. • Several additional parameters were provided by For example, Co Octahedral has an atomic number Dr. Jay Ponder, author of the TINKER pro- of 27 and six ligands. Therefore the atom type gram. number is 276. • Some commonly used parameters that were not In a case where different atom types of the same provided by Dr. Allinger or Dr. Ponder are pro- element have the same number of ligands (Iridium vided by CambridgeSoft Corporation. How- Tetrahedral, Atom Type # 774 and Iridium Square ever, most of these parameters are estimates Planar, Atom Type # 779), the number nine is used which are extrapolated from other parameters. for the second geometry. The best source of information on the MM2 Viewing Parameters parameter set is Molecular Mechanics, Burkert, Ulrich To view the parameters used by Chem & Bio 3D and Allinger, Norman L., ACS Monograph 177, 11.0 to perform MM2 computations, go to American Chemical Society, Washington, DC, View>Parameter Tables>MM2 Atom Type Parameters. 1982. A method for developing reasonable guesses for Editing Parameters parameters for non-MM2 atom types can be found You can edit the parameters that come with in “Development of an Internal Searching Algo- Chem3D. Parameters that you add or change can rithm for Parameterization of the MM2/MM3 be guesses or approximations that you make, or Force Fields”, Journal of Computational Chemis- values obtained from current literature. try, Vol 12, No. 7, 844-849 (1991).

Chem & Bio 3D 235 User Guide , J. , J. Dynamics of Proteins and Nucleic Acids termswith a fifth-order polynomial switching function sary •charge-dipole A interaction term • term quartic A stretching • der Waals for Cutoffs electrostaticvan and •calculation when neces- pi system Automatic For a description and review of description a dynam- molecular and review For see ics, Andrew McCammon and Stephen Harvey, Cam- Andrew McCammon and Stephen Harvey, Cambridge, UK, 1987. Press, bridge University con- this book focus on biopolymers, Despite its tains a cogent description dynamics of molecular as information as well appli- methods, related and cable to other molecules. Charge-Dipole Interaction Term Interaction Charge-Dipole potentialtwo function one of includes Allinger’s possible electrostatic terms:basedone on bond partialon or one based charges. atomic dipoles, The addition of a charge-dipole interaction term where partialfor a combined approach, allows and charges are represented as bond dipoles, phosphate, or as ammonium such chargedgroups, charges. point are treated as Term Quartic Stretching of a quarticWith the addition bond stretching term, ener- stretching bond troublesome negative long appear when bonds are treated by gies which eliminated. are field force Allinger’s The quartic termbond stretching pri-is required itno hasmarily for molecular dynamics; littleor energy effect on low conformations. precisely reproduce energies obtained with To field, set the quartic force con- stretching Allinger’s to zero. Constants table window stant in the MM2 Allinger’s Force Field Force Allinger’s TheAllingerthe Chem3D implementation of areas: these in Field differs Force . Molecular , 791-816 (1995)). Computational Chem- Computational . 16 , J. Comput. Chem. J. View>Parameter Tables>Torsional Parameters Tables>Torsional View>Parameter , by U. Burkert and N. L. Allinger, ACS, ACS, Allinger, L. Burkertand N. U. , by Before performing any editing we strongly recom- strongly we editing any performing Before , by T. Clark, Wiley, N.Y., USA, 1985, also con- also USA, 1985, N.Y., Clark, Wiley, T. , by 236 parameter table. Be sure that the name for parameter table. the duplicated elsewhere in the is not parameter table. For a review of MM2 applicationsand a review of molecu- For methods in general,lar mechanics see Mechanics USA, 1982. D.C., Washington, istry molecular description of tains an excellent mechanics. system and the TINKER the a description of For theto additions for Ponder’s detailed rationale home page force field, visit the TINKER MM2 at http://dasher.wustl.edu/tinker The MM2 Force Field The MM2 Force 11.0 includes a new implementa- Chem & Bio 3D MM2 force field tion of NormanL. Allinger’s W. Jay by done based in largemeasure on work This appendix University. of Washington Ponder MM2 the attempt to completely describe does not the in which the way discusses field, but force in used and implemented force field is MM2 Chem3D this imple- and the differences between MM2 program(QCPE 395), mentation, Allinger’s Dudek and (M.J. TINKER system Ponder’s and Ponder, J.W. NOTE: directory. C3DTable located in the parame- parameter to the Torsional add a new To ters table 1. Go to In addition, there are several adjustable parameters parameters adjustable are several there In addition, table. MM2 Constants in the available 2.of the field data in each Enter the appropriate 3. the table. Close and Save mend that you create copiesmend that you files of all the parameter back-up

Administrator Electrostatic and van der Waals Cutoff Terms erocycle parameters according to G.D. Zeiss and The cutoffs for electrostatic and van der Waals M.A. Whitehead, J. Chem. Soc. (A), 1727 (1971). terms greatly improve the computation speed for The SCF computation yields bond orders which large molecules by eliminating long range interac- are used to scale the bond stretching force con- tions from the computation. stants, standard bond lengths, and twofold torsional barriers. To precisely reproduce energies obtained with Allinger’s force field, set the cutoff distances to A step-wise overview of the process used to per- large values (greater than the diameter of the form pi system calculations is as follows: model). 1. A matrix called the Fock matrix is initialized to The cutoff is implemented gradually, beginning at represent the favorability of sharing electrons 50% of the specified cutoff distance for charge and between pairs of atoms in a pi system. charge-dipole interactions, 75% for dipole-dipole 2. The pi molecular orbitals are computed from the interactions, and 90% for van der Waals interac- Fock matrix. tions. Chem3D uses a fifth-order polynomial 3. The pi molecular orbitals are used to compute a switching function so that the resulting force field new Fock matrix, then this new Fock matrix is is second-order continuous. used to compute better pi molecular orbitals. Because the charge-charge interaction energy 4. Step 2 and step 3 are repeated until the computa- between two point charges separated by a distance tion of Fock matrix and the pi molecular orbitals r is proportional to 1/r, the charge-charge cutoff converge. This method is called the self-consis- must be rather large, typically 30 or 40Å. The tent field technique or a pi-SCF calculation. charge-dipole, dipole-dipole, and van der Waals 5. A pi bond order is computed from the pi molec- 2 3 6 energies, which fall off as 1/r , 1/r , and 1/r , ular orbitals. respectively, can be cut off at much shorter dis- 6. The pi bond order is used to modify the bond tances, for example, 25Å, 18Å, and 10Å, respec- length (BL ) and force constant (KS ) for each tively. Fortunately, since the van der Waals res res sigma bond in the pi system. interactions are by far the most numerous, this cutoff speeds the computation significantly, even for 7. The values of KSres and BLres are used in the relatively small molecules. molecular mechanics portion of the MM2 computation to further refine the molecule. Pi Orbital SCF Computation To examine the computed bond orders after an Chem3D determines whether the model contains MM2 computation: any pi systems, and performs a Pariser-Parr-Pople pi orbital SCF computation for each system. A pi 1. In the Pop-up Information control panel, select system is defined as a sequence of three or more Bond Order. atoms of types which appear in the Pi Atoms table 2. Position the pointer over a bond. window (PIATOMS.xml). The information box contains the newly computed The method used is that of D.H. Lo and M.A. bond orders for any bonds that are in a pi system. Whitehead, Can. J. Chem., 46, 2027 (1968), with het-

Chem & Bio 3D 237 User Guide 238

Administrator Appendix I: MOPAC

This section provides additional information about All are SCF (Self Consistent Field) methods. Each the MOPAC that has not be covered in other areas function represents an approximation in the math- of the Chem & Bio 3D 11.0 documentation:. ematics for solving the Electronic Schrödinger equation for a molecule. • MOPAC background Historically, these approximations were made to • Potential energy functions allow ab initio calculations to be within the reach of • Adding parameters to MOPAC available computer technology. Currently, ab initio • MOPAC Keywords used in CS MOPAC methods for small molecules are within the reach • Electronic configuration (includes using of desktop computers. Larger molecules, however, MOPAC sparkles are still more efficiently modeled on the desktop using semi-empirical or molecular mechanics MOPAC Background methodologies. MOPAC was created by Dr. James Stewart at the To understand the place that the potential energy University of Texas in the 1980s. It implements functions in MOPAC take in the semi-empirical semi-empirical methodologies for analyzing molec- arena, here is a brief chronology of the approxima- ular models. (MOPAC stands for Molecular Orbital tions that comprise the semi-empirical methods. PACkage.) Due to its complexity and command The first approximation was termed CNDO for line user interface, its use was limited until the mid Complete Neglect of Differential Overlap. The 1990s. next approximation was termed INDO for Inter- mediate Neglect of Differential Overlap, Next fol- Since version 3.5 (1996), Chem3D has provided an lowed MINDO/3, which stands for “Modified easy-to-use GUI interface for MOPAC that makes Intermediate Neglect of Differential Overlap”. it accessible to the novice molecular modeller, as Next was MNDO, which is short for “Modified well as providing greater usability for the veteran Neglect of Differential Overlap” which corrected modeller. We are currently supporting MOPAC MINDO/3 for various organic molecules made up 2002. from elements in rows 1 and 2 of the periodic MOPAC 2002 is copyrighted by Fujitsu, Ltd.CS table. AM1 improved upon MNDO markedly. MOPAC is the licensed version that runs under Finally the most recent, PM3 is a reparameteriza- Chem3D. tion of AM1. The approximations in PM3 are the The MOPAC User Manual, formerly included on same as AM1. the Chem3D CD-ROM in PDF format, is now This sequence of potential energy functions repre- available as WebHelp at: http://www.cachesoft- sents a series of improvements to support the ini- ware.com/mopac/Mopac2002manual/index.html. tial assumption that complete neglect of diatomic orbitals would yield useful data when molecules Potential Energy Functions proved too resource intensive for ab initio methods. MOPAC provides five potential energy functions: MINDO/3, MNDO, PM3, AM1, and MNDO-d.

Chem & Bio 3D 239 User Guide min- to turn turn to BFGS NOMM ) minimizer. EF and restores the EF Automatically sent to MOPAC to sent to MOPAC Automatically cor- Mechanics specify Molecular Use the rection for amide bonds. additional keyword The calculated/predicted energy be less than n.nn.change must Thedefault is 4.0. The calculated/predicted energy be morethanchange n.n. must The is 0.000. default value a calculations using the SCF Runs do higher precisionthat so values not fluctuaterun from to run. to make Overrides checks safety jobthe run faster. if the optimiza- Use this keyword to a troubletion converging has transition state. Automatically sent to MOPAC to sent MOPAC to Automatically Eigenvector specify the use of the ( Following insertion the automatic Prevents of to sent MOPAC to Automatically of the Z- checking override matrix. this keyword off. keyword this imizer. MMOK RMAX=n.nn RMIN=n.nn PRECISE LET RECALC=5 Keyword Description EF BFGS GEO-OK Automatic Keywords Automatic automatically keywords contains The following you keywords additional and some MOPAC sent to affect convergence. to can use CAUTION http://www.cachesoft- tab of the MOPAC Interface. You can edit You Interface. MOPAC tab of the . 240 Use the automatic keywords unless you are an you unless automatic keywords the Use Changing the keywords user. MOPAC advanced unreliable results. give may MOPAC the see complete list of keywords a For online manual. Selecting parameters for a MOPAC approximation approximation Selecting parametersMOPAC for a on the in a window automatically insertskeywords General Using Keywords Parameters are in constant development for use development are in constant Parameters find If you functions. potentialAM1 with PM3 and that the standard with that comes set of parameters CS you that an element not cover does MOPAC the literature can search example Cu, you need, for for the necessaryit at run parameter and add time Thisflexibility job. when performing a MOPAC greatly of MOPAC. enhances the usefulness at run can add parameters key- time using the You the where name is EXTERNAL=name, word its full path)name of the file (and containing the additional parameters. A description of the required formatfor this file can be found at: ware.com/mopac/Mopac2002manual/node177.ht ml Adding Parameters to MOPAC to Parameters Adding these keywords or use additional keywords to per- keywords or use additional these keywords form informationcalculations other or save to the *.out file.

Administrator For descriptions of error messages reported by The following table contains the keywords that MOPAC see Chapter 11, pages 325–331, in the invoke additional computations. Terms marked MOPAC manual. with an asterisk (*) appear in the *.out file. Additional Keywords Keyword Description Keywords that output the details of a particular computation are shown in the following table. CIS UV absorption energies* Terms marked with an asterisk (*) appear in the Performs C.I. using only the first *.out file. excited Singlet states and does not include the ground state. Use Keyword Data MECI to print out energy information in the *.out file. ENPART All Energy Components* FORCE Vibrational Analysis*Useful for FORCE Zero Point Energy determining zero point energies * and normal vibrational modes. FORCE Vibrational Frequencies Use DFORCE to print out vibra- MECI Microstates used in MECI calcu- tion information in *.out file. * lation NOMM No MM correction By default, none HOMO/LUMO Energies* MOPAC performs a molecular mechanics (MM) correction for none Ionization Potential* CONH bonds. * none Symmetry PI Resolve density matrix into sigma and pi bonds. LOCALIZE Print localized orbitals PRECISE Increase SCF criteria VECTORS Print final eigenvectors (molecular orbital coefficients) Increases criteria by 100 times. This is useful for increasing the BONDS Bond Order Matrix* precision of energies reported.

T = n [M,H,D] Increase the total CPU time allowed for the job. The default is 1h (1 hour) or 3600 seconds.

Specifying the Electronic Configuration MOPAC must have the net charge of the molecule in order to determine whether the molecule is open or closed shell. If a molecule has a net charge,

Chem & Bio 3D 241 User Guide C.I.=n

ROOT=n

a OPEN(n1,n2) Use for high symmetry for high symmetry

DOUBLETTRIPLET 1,2 QUARTETQUINTET 2,2 3,3 SEXTET 4,4 DOUBLET 5,5 TRIPLETQUARTETQUINTETSEXTET 2DOUBLET 2 2 2 TRIPLET 2QUARTET 3 QUINTET 4 2SEXTET 5 3 6 3 3 3 3 3 4 3 5 6 Spin State Keywords to state systems except state systems shells with open systems Do not use OPEN(n1,n2) for ground- a. electrons. state. UHF (Open Shell) • of number an odd or Thehas an even molecule • Theits groundin is molecule an excited state or • methods. UHF or use RHF To Ground SINGLET 1st Excited SINGLET2nd Excited 2 SINGLET 3 Electronic Electronic State 22 1/2 QUINTET SEXTET 4 unpaired 5 unpaired RHF (Closed Shell)RHF (Closed To determine the appropriate spin multiplicity, determine multiplicity, the appropriate spin To consider whether: permu-common some shows table The following of these three factors:tations and choose a and choose box, type the electrons) Keywords iplicity of the molecule. of the molecule. iplicity , where n is a positive or , where n is a positive tab, in the the in tab, CHARGE=n General Calculations>MOPAC Interface Calculations>MOPAC 242 negative integernegative (-2, -1, +1, +2). calculation. The MOPAC Interface dialog box Interface dialog box Thecalculation. MOPAC appears. keyword keyword 0SINGLET0 unpaired unpaired Spin Keyword0SINGLET0 (# unpaired 1/21TRIPLET2 DOUBLET1 1/2 1 unpaired QUARTET 3 unpaired Different combinations of spin-up (alpha elec- spin-up Different combinations of (beta lead to vari- electrons) trons)and spin-down These combinations are electronic energies. ous specified as the Spin Mult between the relation table shows The following of and the number spin multiplicity, total spin S, unpaired electrons. 2. On the be sure you have either specified a charged atom specified either have you be sure charge. theor added type supports 2002 “sparkles”– ionic pure MOPAC CS to or charges counter-ions that can be used as form effects. solvation that mimic dipoles Building a charge the Text using can assign You MOPAC: specifying it in by tool or add the charge to the model: To 1.Building tool. the Text Click 2.model. an atom in your Click 3. a charge symbol. Type carbon and type “+” in a text a click example, For it a carbocation.The charge to make is auto- box do a calcula- when you matically sent to MOPAC tion. specify the chargein MOPAC: To 1. Go to

Administrator Ground State, UHF Electronic State Spin State Ground SINGLET For UHF computations, all unpaired electrons are DOUBLET forced to be spin up (alpha). TRIPLET • Singlet ground state—the most common con- QUARTET QUINTET figuration for a neutral, even electron, stable SEXTET organic compound. No additional keywords are necessary. Even-Electron Systems • UHF will likely converge to the RHF solution If a molecule has an even number of electrons, the for Singlet ground states. ground state and excited state configurations can • Triplet or Quintet ground state: Use the key- be Singlet, Triplet, or Quintet (not likely). Nor- word TRIPLET or QUINTET. mally the ground state is Singlet, but for some molecules, symmetry considerations indicate a Triplet is the most stable ground state. NOTE: When a higher multiplicity is used, the UHF solution yields different energies due to separate treatment of Ground State, RHF alpha electrons. The Ground State, RHF configuration is as follows: Excited State, RHF Singlet ground state. the most common configuration for a neutral, even electron stable organic First Excited State: The first excited state is actually compound. No additional keywords are necessary. the second lowest state (the root=2) for a given spin system (Singlet, Triplet, Quintet). Triplet ground state. Use the following keyword combination: TRIPLET OPEN(2,2) To request the first excited state, use the following sets of keywords: Quintet ground state. Use the following keyword First excited Singlet: ROOT=2 OPEN(2,2) SINGLET combination: QUINTET OPEN(4,4) (or specify the single keyword EXCITED) First excited triplet: ROOT=2 OPEN (2,2) NOTE: The OPEN keyword is normally necessary only TRIPLET C.I.=n, where n=3 is the simplest case. when the molecule has a high degree of symmetry, such as ROOT=2 OPEN (4,4) QUIN- molecular oxygen. The OPEN keyword increases the active First excited quintet: TET C.I.=n, where n=5 is the simplest case. space available to the SCF calculation by including virtual orbitals. This is necessary for attaining the higher multiplicity Second Excited State: The second excited state is configurations for even shell system. The OPEN keyword actually the third lowest state (the root=3) for a also invokes the RHF computation using the 1/2 electron given system (Singlet, Triplet, Quintet). To request approximation method and a C.I. calculation to correct the the second excited state use the following set of final RHF energies. To see the states used in a C.I. calcula- keywords: tion, type MECI as an additional keyword. The information Second excited Singlet: OPEN(2,2) ROOT=3 SIN- is printed at the bottom of the *.out file. GLET Second excited triplet: OPEN(2,2) ROOT=3 TRIP- LET C.I.=n, where n=3 is the simplest case.

Chem & Bio 3D 243 User Guide , , , , ET C.I.=n is printed at the bottom of ROOT=3 DOUBLET DOUBLET ROOT=3 ion, type MECI as an addi- ROOT=3 QUARTET C.I.=n QUARTET ROOT=3 ROOT=3 SEXT ROOT=2 QUARTET C.I.=n ROOT=2 SEXTET C.I.=n SEXTET ROOT=2 sium or cesium cation + electron cesium cation + sium or Equivalent to... If you get an errorIf you active indicating the spaceis not , where n=3 is the simplest case. is , where n=3 Chemical symbol +++ ammonium, potas- tetramethyl barium di-cation + 2 electrons where n=5 is the simplest case. case. simplest the is where n=5 The State: state is second excited Second Excited (the root=3) for a state third lowest actually the request To Quintet). (Singlet, Triplet, system given of set the following use state excited the second keywords: doublet: Second excited where n=4 is the simplest case. the where n=4 is sextet: Second excited NOTE: the *.out file. UHF Excited State, can be multiplicity Only the ground state of a given calculated using UHF. Sparkles Sparkles are used to represent pure ionic charges. chem- following the to Theyroughly equivalent are ical entities: C.I.=n quartet: Second excited where n=5 is the simplest case. the where n=5 is spanned, for the simplest use C.I.> n to increase case the in the number of orbitalsactive available seespace. the To C.I. calculat used in a states The informationtional keyword. where n=4 is the simplest case. simplest the n=4 is where sextet: First excited First excited quartet:First excited , state: Use the keyword the keyword state: Use keyword combination: keyword OPEN(4,4) ROOT=3 QUIN- (the root=2) for a given given a root=2) for (the . ROOT=2 DOUBLET DOUBLET C.I.=n ROOT=2 SEXTET SEXTET OPEN(5,5) , where n=5 is the simplest case. is the simplest where n=5 , or 244 Excited State, RHF Excited State, actually state is State: Theexcited first Excited First state the second lowest request Quartet,(Doublet, spin system To Sextet). of key- sets use the following state excited the first words. doublet: excited First QUARTET Ground State, UHF State, Ground unpaired electrons are all UHF computations For forced to be spin up (alpha). Doublet groundThis state: most common the is No configuration odd electrona for molecule. are necessary. keywords additional different from those UHF will yield energies method. the RHF obtained by Quartetground and Sextet QUARTET OPEN(3,3) QUARTET Sextet ground keyword state: Use the following combination: Often, anions, cations, or radicals are odd-electronare or radicals cations, anions, Often, groundthe excited states and Normally, systems. quartet can be doublet, state configuration or sextet. RHF State, Ground Doublet groundThis state: most common the is are neces- keywords configuration. No additional sary. Quartet:Use the following Excited State, UHF Excited State, Only canmultiplicity the ground be state of a given using UHF. calculated Systems Odd-Electron Second excited quintet: quintet: excited Second where n=2 is the simplest case. where n=2 TET C.I.=n

Administrator The output file shows the chemical symbol as XX. Chemical Equivalent to... symbol

_ borohydride halogen, or nitrate anion minus electron = sulfate, oxalate di-anion minus 2 electrons Sparkles are represented in Chem & Bio 3D 11.0 by adding a charged dummy atom to the model.

TIP: Dummy atoms are created with the uncoordinated bond tool. You must add the charge after creating the dummy.

Chem & Bio 3D 245 User Guide 246

Administrator Appendix J: Technical Support

CambridgeSoft Corporation (CS) provides techni- Email: [email protected] cal support to all registered users of this software Fax: 617 588-9360 through the internet, and through our Technical Mail: CambridgeSoft Corporation Support department. ATTN: Technical Support Our Technical Support webpages contain answers to frequently asked questions (FAQs) and general 100 CambridgePark Drive information about our software. You can access Cambridge, MA 02140 USA our Technical Support page using the following address: http://www.cambridgesoft.com/services/ Serial Numbers If you don’t find the answers you need on our Web When contacting Technical Support, you must site, please do the following before contacting always provide your serial number. This serial num- Technical Support. ber was on the outside of the original application 1. Check the system requirements for the software box, and is the number that you entered when you at the beginning of this User’s Guide. launched your CambridgeSoft application for the 2. Read the Troubleshooting section of this appen- first time. If you have thrown away your box and dix and follow the possible resolution tactics lost your installation instructions, you can still find outlined there. the serial number. Go to Help>About CS {application name}.The serial number appears at the bottom left 3. If all your attempts to resolve a problem fail, fill of the About box. out a copy of the CS Software Problem Report Form at the back of this User’s Guide. This form For more information on obtaining serial numbers is also available on-line at: and registration codes see: http://www.cambridge- http://www.cambridgesoft.com/services/mail soft.com/services/coderequest/ • Try to reproduce the problem before contact- Troubleshooting ing us. If you can reproduce the problem, please record the exact steps that you took to This section describes steps you can take that do so. affect the overall performance of CS Desktop • Record the exact wording of any error mes- Applications, as well as steps to follow if your com- sages that appear. puter crashes when using a CS software product. • Record anything that you have tried to correct Performance the problem. Below are some ways you can optimize the perfor- You can deliver your CS Software Problem Report mance of CambridgeSoft Desktop Applications: Form to Technical Support by the following methods: • In the Performance tab in the System control panel, allocate more processor time to the Internet: http://www.cambridgesoft.com/ser- application. vices/mail

Chem & Bio 3D 247 User Guide

Try usinga ent driver helps, your your helps, ent driver . If using a different . If using http://www.cambridgesoft.com/services/mail bridgeSoft Desktop Application, try switching Control display in the driver video VGA to the then retest the and System Setup, (or Panel a differ If using problems. be updated–contact need to may original driver up- most obtain the and the driver of the maker contact trouble have still If you driver. to-date details about the original with the relevant us problem. and the resulting driver related problems: Driver Printer different printer driver be need to may driver original your helps, driver and of the driver maker updated–contact the still If you obtainup-to-date driver. the most details trouble contact us with the relevant have and the resulting prob- about the original driver lem. and provide the details of the problem to Tech- the provide and nical Support. uninstall the software and disable all background and disable uninstall the software virus and including screen savers applications, instruc-the complete uninstall See protection. Supporttions the onCambridgeSoft Technical page. web at: • 3. reinstall, Before you reinstalling the software. Try 4.use our contact form problem still occurs, If the If you are If you ware applications, there applications, ware memory extends RAM by allowing space on space memoryallowing by RAM extends hardyour disk to be used as RAM. However, application the between swapping the time for with than swapping and the hard disk is slower RAM. physical have, the less the less Desktop ChemOffice Applica- have, use hard diskto your to access have tions will Virtual Memory. Video Driver related problems: Driver Video Cam-any of problems the display with having 248 lem. If the problem recurs, continue with the fol- with the continue problem recurs, the lem. If steps. lowing and virus pro- savers, screen printer drivers, ers, be sure to do need to contactus, tection. If you you determineof drivers version what type and are using. • Increase the Virtual Memory (VM). Virtual •The RAM. Install physical more you more • Applications and Drivers Applications and most complex soft As with & Chem circumstances in which be unusual may are Below become unresponsive. may 11.0 3D Bio to try to follow you recommended stepsfor some issues. driver and software to resolve 1. tryand Windows to reproduce Restart prob- the 2. The conflicts most common concern video driv-

Administrator Section II: ChemScript

Introduction Object Functionality and Attributes “Chemical Intelligence” algorithms are prevalent Class throughout CambridgeSoft products. A set of these algorithms, called ChemScript, is written in the Reaction A chemical reaction with one or Python scripting language. CambridgeSoft has (Rxn) more steps. made them available through an object model that you can customize for your own use. This means At a higher-level, ChemScript functionality com- that you can use the ChemScript library to design prises various functions and algorithms that are your own scripts to meet your specific business built on the basic object model. Some examples of needs. higher level functionality are listed in the table below (Premium functionality may also be licensed. ChemScript Functionality Contact CambridgeSoft for information): Functionality in ChemScript Enterprise is divided into two levels. At one level, ChemScript provides Functionality Description access to a chemistry object model that includes the basic objects and attributes shown in the table Template based Enforce standard represen- below. These objects provide an easy-to-use inter- normalization tations of functional group face to chemical data for modifying the code. structures in chemical data. Template based Automatic generation of product genera- products from a set of reac- Object Functionality and Attributes tion tants and a generically Class defined reaction. For example, reactions like those Atom Chemical element, charge, bonds between amines and carbox- to neighboring atoms, drawing ylates. coordinates, 3D coordinates (if available), stereochemistry, etc. Substructure Atom-by-atom comparison identification of a molecule with a sub- Bond Bonded atoms, bond order, etc. and mapping structure. Positive matching provides an atom-by-atom Molecule A chemical connection table map of the substructure (Mol) which can represent one or more atoms to those in the mole- molecular fragments. This class cule. also includes file I/O capabilities Salt stripping Removal of salts from a and other advanced chemistry reaction based on a pre- functionality such as stereochem- defined list of salt fragments. istry.

ChemScript 249 User Guide Script API guide. This guide. Script API ript and Python y of documents and exam- of documents y Getting Started Installing ChemSc the Chem- install ChemScript, double-click To in the distri- Script installer that has been provided bution. Once installed, ChemScript will place a folder underneath Start This the Windows menu. variet folder contains a ple files. Developing Scripts The can create scripts using any text editor. You Python includes the Inte- of version Windows grated(IDLE), an Environment Development Learning ChemScript introduction to Chem- a basic provide Here we of ChemScript examples Script and offers several programsperformthat tasks. useful but simple includes example a brief explanation and the Each to write ChemScript functionality that is used. So, more sophisticated programswith ChemScript, find it necessarymay to study the languageyou in moderate detail. also introduce the Chem We and attributes, classes, all of the describes guide in ChemScript. methods that are available already existingalready installationPython, providing of with is compatible 2.4. ThePython that the version of set a rich developed has Python community at the Python extensionsto Python, freely available These database site. extensions provide home Web functionality, server-side Web connectivity, GUI fea- processing, languagenumeric interop, needed is that else and just about anything tures, for development. software rapid more informationfind can on Python at: You In addition, there are http://www.python.org. many bookslanguagePython aboutthe that are available. Optimize molecular struc-Optimize molecular force- the MM2 tures using field. Generate unique identifying struc-from a chemical codes ture. write file data and Read using all CambridgeSoft supported file formats (CDX, CDXML, MOL, CHM, etc.) SMILES, SKC, struc-a chemical Generate name; chemical ture from a name generatea chemical structure. from a chemical * Description orientationEnforce standard of structuresthe based on established orientation of a scaffold. common 11.0- Use Chem & Draw Bio algorithmsbased to provide structure diagram generation or after modi- from scratch data. fying chemical 250 Name and structure conversion Molecular mechanics File format conversion Canonical codes Structure orientation 2D structure and generation cleanup Functionality About Python anonPython proprietary is pro- and widely used gramming clear syntax, It provides language. object-oriented programming, dynamic datatyp- anding,performance high range across a broad of for the ChemScriptplatforms. 10.1 is designed platformWindows basedand on Python 2.4. is CambridgeSoft Python 2.4 alongprovides with ChemScript. Users can installChemScript onto an In addition to using pre-built higher level function- In addition to using pre-built higher level func- level higher own can create your you ality, tions and algorithmsof on top the basic object module.

Administrator easy-to-use system that you can use to edit, exe- 1. Open any one of the script.py files in a text edi- cute, and debug Python programs. You can also tor so that you can either print it or view it on use IDLE as an effective way to develop Chem- screen. Script programs. Other development environ- 2. Examine the input files either in a text editor or ments that are available for Python include another program such as ChemDraw or Chem- ActivePython, which provides more advanced Finder where you can view the chemical struc- functionality. You can even develop simple Python tures. programs using an editor such as Windows Note- 3. Execute the script file. Pad. After you create a python program, you can 4. Examine the output files. launch it from the command line or by double- clicking the script Windows icon. Example 1: Read a list of files, perform Interactive Mode structure cleanup, write a list of files You can use Python in an interactive mode, similar This script lets you import multiple CDXML files, to various mathematical programs that are avail- clean up structures stored in them, and then save able. In interactive mode, you can type and execute the updated files. The script also deals with possi- statements one by one. The results of the state- ble error conditions such as non-existent files and ments can then be examined by the user. Start the bad data (when executed, the script intentionally interactive mode by double-clicking the Python.exe triggers these errors). For simplicity, the filenames file in the Python distribution. This file is also are stored in an array. available in the IDLE development environment. This example also illustrates how ChemScript automatically identifies the structure file format ChemScript Examples (such as MDL MOL) by examining the filename extension. The example is intentionally limited to The ChemScript includes a small set of simple identify only the format. Although not present in example files that demonstrate some of the fea- this example, It is also possible to be more explicit tures of ChemScript. If you have installed Chem- and force ChemScript to use a particular data for- Script using the default settings, you can find these mat for reading and writing chemical data. files at: C:\Program Files\CambridgeSoft\ChemScript Example 2: Read a list of files, write an 10.1\Samples SD file Each example is completely contained in its own directory. For instance, the first example is located This script lets you read multiple files and save in the directory Example.001. For each example, the their content in a single SD file. The script also script file is named script.py. Typically, input data is demonstrates exception-based error handling (you located in the "Input" directory inside the example must explicitly enable it). directory. (each script creates its own output direc- Example 3: Read an SD file, write a list tory when you run it). of CDXML files This section provides a brief explanation of what each example does. Follow the procedure below to This script is essentially the reverse of Example 2. learn about the example files: It demonstrates the ability to read an SD file. The MIME type for data output is explicitly set to

ChemScript 251 User Guide n in this example, the n in this example, t the salt component, and table that enables the pro- table Example 8: Basic salt stripping usagebasic This a of the salt strip- example shows ping functionalityThe in ChemScript. program salt com- and removes identifies SD File, an reads SD outputs two ponents (if any are present), and structuresinput Not all of the contain a salt files. component. Theoutput structures file contains the original structures withou the output salt file contains the saltcomponents stripped, along with a reference to that the were ID of the original structure. Although can innot you also this shown example, salt define a customized are consid- grammerchemicals to designate which This of salts a default set example uses salts. ered Example 7: Read an SD file, perform a Example 7: Read group), (nitro transformation reaction write an SD file Thisreaction a basic use of example demonstrates transformationChemScript. trans-in chemical A formationareaction as can be that is drawn applied to an input structure, resulting in modified output structure. the reaction transfor- In this case, a particular of rep- the conversion specifies mation nitroresentationthe group of a different into representation. Thetransformation reaction is contained in the file transform1.cdxml in the input structuresthe Note that some of in the directory. the transformation unaffected by remain input file do not containthey the appropriately because represented nitro group. two chemically similar structures chemically two superim- to be the programexample, In this posed. a processes set of structuresthat contain a common scaffold substructure, these structures and aligns so that the same orientation to with respect the they have scaffold.(Although not show be used can also functionality to align overlay structures.) three-dimensional file, filter based file, filter cal codes, write a cal codes, write ctures. In this case, the In this case, ctures. for reading an SD file. for reading an SD ite two SD files o output SD files based 252 This fea- program the structureintroduces overlay for allows Structureture in ChemScript. overlay Example 6: Read an SD file and scaffold, align scaffold, write an SD file single SD file Example 5: Read two SD files, check for Example 5: Read canoni duplicates using This example introduces the ability to compute the canonical code for moleculara structure. The canonicalcode does vary not with different repre- structure,can chemical so it same the of sentations be used to determinestructures whether two are equivalent. chemically This example also introduces the Python Dictio- The dictionary array. an associative is which nary, to a value. key maps a writes a single and The SD files, programtwo reads The input files containoutput SD file. dupli- some The programcate structures. merges and files the eliminates any duplicate stru key is a canonical code, and the dictionarythe and is a canonicalcode, key is used to determine has been encoun- a canonical code if that this example uses an Note previously. tered alternate looping construct Example 4: Read an SD Example Thisof application example demonstrates a simple substructurethe "atom-by-atom" in Chem- search Script. The program reads an SD file and filters structures tw one of into structureon whether the group. a phenyl contains data for- ability the read chemical to It also shows string. matted as a SMILES 'text/xml', forcing the generation forcing 'text/xml', data of CDXML output. Thein the sup- for other types MIME porteddata formats doc- reference in the are listed umentation. wr on substructure,

Administrator provided by CambridgeSoft. There is a rich set of ality. There is also a convenience function that pro- options associated with the salt stripping function- tonates a charged structure.

ChemScript 253 User Guide 254

Administrator Section III: ChemFinder & BioViz

About ChemFinder 11.0® based on values of selected properties. See “Com- pound Profiles” on page 389. ChemFinder 11.0 is a database management system Embedded controls. In a ChemFinder 11.0 form, for anyone who works with chemical information. you can add a box for a third-party ActiveX control. It provides a place to store chemical structures, See “Embedding ActiveX controls” on page 429 physical properties, notes, tables of data, and charts for more information. based on that data. It takes the place of that box of index cards you’ve been using to jot notes about in- ChemFinder 11.0/Python®. ChemFinder 11.0 teresting molecules and reactions, but does it much includes an embedded Python interpreter. The pop- better! With ChemFinder 11.0, you can search ular, full-featured programming language is now through data efficiently and quickly, and you can or- available to you from within ChemFinder 11.0 for ganize the data instantly. OLE Automation, file I/O, and many other applications. See “Scripting Part II: Python™” on page About BioViz 432 for more information. BioViz is a visualization add-in for ChemFinder CFX file format. ChemFinder 11.0 forms have a 11.0 that allows you to plot numeric data in Chem- new file extension: .cfx. These files are in XML for- Finder 11.0 databases. You can identify trends and mat, readable and editable in Notepad or any XML correlations in your data, and within subsets of your editor. CFX files produced by ChemFinder 11.0 will data, without the extra step of exporting to another be compatible with all future ChemFinder versions. application. You can have as many plot windows as CFW files are still supported. You can open old you like, each showing a different visualization of CFW files, and save to that format using the Save As data from the current form. File menu command, however many new features ChemFinder 11.0 & BioViz are integrated with the are not supported in the older format. following CambridgeSoft products: Enhancements • ChemDraw® Find Structures menu. The Search>Find Structures ® • Chem3D submenu has been enhanced in ChemFinder 11.0 • ChemDraw/Excel® to include searches for ring types, charged struc- ® tures and radicals. See “Special structure searches” • ChemOffice 2006 on page 362 for more information. What’s new in ChemFinder 11.0? UI enhancements. • Style button for text and frame boxes ChemFinder 11.0 includes the following new features: • Read-only structure box option Compound profiles. This new feature offers a • Automatic frame label updates way of visually comparing and ranking structures R-Group tables. R-Group tables can now be sort-

ChemFinder & BioViz 255 User Guide ed. R-Group structures can be copied with the clip- cannot be sorted like other fields by the data- board. See “R-group tables” on page 326 for details. base server. “Loose delocalization” search mode. Chem- NOTE: Because of the complexity, you are prohibited from Administrator Finder 11.0 defines “delocalized” as cyclic alternat- choosing both formula and molweight as components in the ing single/double bonds. If the default algorithm same sort operation. does not produce the hits you want, you may select Import/Export options. A number of improve- an algorithm which more or less ignores labile elec- ments affect both ChemFinder 11.0 and Oracle da- trons in query and targets, thus delivering more hits tabases. See “Importing data” on page 373, for queries involving potential tautomeric or delo- “Exporting data files” on page 378, and “Exporting calized bonds. See “Normalization” on page 455 to an Excel spreadsheet” on page 421. for more details. Database enhancements. Picture boxes can con- MS Office 2007 support. The ChemFinder 11.0 nect to fields with bitmap graphical data, not just MS Word export option may be used with Word Windows Metafiles. You can now read in picture 2007 data directly from databases containing such files. Sort improvements. See also “R-group tables” on In addition, floating point values (double fields) can page 326 and “Sorting by subform value aggregate” serve as ID fields. This corrects a functionality on page 410. problem with tables in some databases. •Stable sort Oracle/BioSAR enhancements. When sorting a field containing duplicates, CAL enhancements. Three new commands. See sorting is called “stable” if a consistent order is “New in ChemFinder 11.0” on page 469 for details. maintained within each block of duplicates. ChemFinder 11.0 sorts are now stable when- What’s new in BioViz 11? ever possible. This is done by automatically ® specifying an ID field (Mol_ID or other pri- BioViz includes the following new features: mary key, if such a field exists in the data table) Plot appearance controls. Users can now cus- for the secondary sort order. tomize point shape and size, background color, axes •Subform sorting labels, and more. See “User-customizable styles” on Sorting within a linked subform has been dis- page 395. abled. The sort order was not preserved as you Subform plots. Subform boxes can now be shown browsed records of the main form, which as a plot made from the fields of the table connect- users found confusing. ed to that subform. This allows quick visualization •Multiple sorting of the data in a subform on a per-compound basis. The Sort>Multiple... (Sort Column>Multiple... in See “Subform plots” on page 387. Table view) context menu dialog box now Enhancements includes the Formula and MolWeight fields. These fields are special because they are not • Improved statistical display actually stored in the database, and therefore • Improved histogram bar coloring • Extended state-saving

256 ChemFinder 11.0/Oracle The Ultra symbol indicates that a feature enhancements is available in the Ultra version only. BioSAR integration. You can now export data forms from BioSAR directly into ChemFinder 11.0 The Pro symbol indicates that a feature is by means of an Oracle database. available in both the Pro and Ultra versions. • UI Improvements Features that are available in the Standard version are not indicated by a symbol. • Control box Special formats About this user’s guide Cautions are used to warn you of situations that might This User’s Manual contains information for the cause a possible loss of data. ChemFinder & BioViz 2007 desktop application for Windows. It assumes that you are familiar with the basics of your Windows operating system. If NOTE: Notes are used to highlight important information. you are not, please refer to your system manual be- TIP: Tips are used to present information supplemental to fore using the applications. Some of the material de- the main text. scribes tasks that must be performed in conjunction Shortcut key sequences are indicated with a + sign, with other integrated CambridgeSoft products. The for example: “Use the command: Ctrl+H to toggle material on the Addins describes tasks that must be hidden Hydrogens and lone pairs.” performed in conjunction with Microsoft Excel or A bold font is used to refer to the User Interface, Word. If you are not familiar with these products, for example “... click the File>Save menu com- please consult the relevant User’s Manual for more mand”. detailed information. The chapters in this guide are organized by task. Additional information They are intended to help you familiarize yourself with the ChemOffice applications and start using Additional sources of ChemOffice information are: them as quickly and efficiently as possible. New us- • The Quick Reference Cards. ers should read the Basics chapter to get an over- • The Help system view of the product and how it works. The Tutorials chapter demonstrates most of the features of the • CambridgeSoft Web Pages. application. Perform the tutorials in the order they http://CambridgeSoft.com/services are presented. Experienced users can skip to subse- Quick reference card quent chapters, which provide more detailed information. The ChemOffice Quick Reference Cards are located in the back of the manual. The cards provide Conventions summaries of ChemOffice Desktop Application The following notations are used throughout this commands and features. Because many of the in- user’s guide: structions require knowledge of the interface elements, use the Quick Reference card as you perform the tutorials in Chapter 2: Tutorials.

ChemFinder & BioViz 257 User Guide Help system activation each time you access the page. If you visit a site frequently, you can add it to the list of ChemOffice applications provide some or all of the trusted sites in IE’s security settings. following types of Help: Administrator • Help—An HTML reference guide. Site license network installation • Context-sensitive Help— Help topics related instructions to user interface objects. To access Context If you have purchased a site license, please see the sensitive Help type Shift+F1. following web site for network installation instruc- • ToolTips—Short descriptions of user interface tions: objects displayed by pointing. http://www.cambridgesoft.com/services/Desk- • Status Bar—The lower left corner of the GUI topSupport/Documentation/NetworkInstalls/ displays useful information as you work. CambridgeSoft web pages Installation and system The following table contains the addresses of requirements ChemDraw-related web pages. Before installation, see the “ReadMeFirst” and any other ReadMe documents on the installation CD- For information Access … ROM. about …

Microsoft® Windows® requirements Technical http://www.cambridge- Support soft.com/services • Windows 2000 or XP Pro •Microsoft® Office add-ins require Office 2000, ChemDraw Plug- http://www.cambridge- 2003, or XP in soft.com/services/Desktop- • Screen resolution must be 800 x 600 or higher. Support/Documenta- tion/Plugins/ ChemDraw plug-ins/ActiveX® controls support Microsoft IE 6.x and 7.0, Netscape® 7.x and 8.x, Chem3D ActiveX http://www.cambridge- Mozilla 1.x, and Firefox 1.x and 2.0. control soft.com/services/Desktop- The Chem3D ActiveX control supports Microsoft Support/Documenta- IE 6.x and 7.0, Netscape® 7.x and 8.0, Mozilla 1.x, tion/Plugins/ and Firefox 1.x and 2.0. NOTE: Windows XP Service Pack 2 includes security fea- Software Devel- http://www.cambridge- tures that automatically block active content. This means oper’s kit soft.com/services/documen- that by default, Internet Explorer blocks ChemDraw and tation/sdk/ Chem3D ActiveX controls. To activate them, you must choose the option to “allow blocked content” from the bar Purchasing http://scistore.cambridge- appearing under the address bar notifying you that the secu- CambridgeSoft soft.com/ rity settings have blocked some of the content of the page. IE products does not remember this information, so you must repeat the

258 ChemFinder & BioViz 259 User Guide Administrator

260 Chapter 13: The ChemFinder 11.0 User Interface

Overview For information on BioViz see “Visualizing Data With BioViz” on page 395 and “Tutorial 6:BioViz ChemFinder 11.0 is a database management system quickstart” on page 288. that allows storage, retrieval, and searching of mo- The general steps for using ChemFinder 11.0 are as lecular structures, text, and numerical data. follows: You create structures in ChemDraw or with the built- in ChemDraw ActiveX control to store in your • Create a form. ChemFinder 11.0 database, and add related numer- • Create or open a database and link it to the ical or textual data and comments. You can use the form. Chem3D ActiveX control to view the structures. • Add or manipulate data. Use ChemFinder 11.0 as a reference, together with • Perform a search. one of the CD-ROM databases provided. Use it as your corporate database system, available to anyone These steps are described in the ChemFinder 11.0 on your network. Use it as a registration system or Tutorials, and in the detailed reference material in front-end search engine for your big mainframe da- the manual. tabase. Use it as a custom viewer for your Oracle data, with or without chemical structures. Use it to The ChemFinder 11.0 UI keep track of what you find in your routine litera- The ChemFinder 11.0 UI consists of menus, tool- ture scans. Use it to make a database to keep the fig- bars and the form window. The central part of the ures that go in your thesis or your next paper. form window contains the work space where you This chapter describes the ChemFinder 11.0 & Bio- create and view structures and data. The toolbars Viz user interface (UI), including each of the Chem- contain icons that change the way the pointer be- Finder 11.0 toolbars, and the status bar. Following haves or that perform actions corresponding to that is a description of UI improvements in Chem- menu commands. Finder 11.0, a brief description of opening a data- The components of the ChemFinder 11.0 UI are base, using a database, and finally a discussion of the ChemFinder 11.0 database model.

ChemFinder & BioViz 261 User Guide shown in Figure 1.

Main toolbar Title bar Record toolbar Search toolbar Text Format toolbar

Administrator Menu bar Main form (tabbed) Structure box Text box (shows current Picture box record) Framed data box Form toolbar Subform

Explorer window (Database panel Profiles box visible) Main form tabs

Filter window BioViz Details window window

Structure window (shows BioViz moused point)

Favorites tab Output Queries tab window Database tab Total status bar db size

Read-only New record Query Current Current indicator indicator indicator record list size

Figure 13.1 The ChemFinder 11.0 user interface The components of the ChemFinder 11.0 UI are Screen Element Description described below Current list size Displays the number of records Screen Element Description through which you are browsing. Might be less than the total database size if you have BioViz window Displays plotted data from recently performed a search. ChemFinder 11.0 databases. Current record Displays the position within the current hit list of the record you are viewing.

262 Screen Element Description Screen Element Description

Control box A data box containing an Form toolbar Contains icons representing the ActiveX control. form-creation tools available in ChemFinder 11.0. Click a tool Details window Displays details of selected (or icon to select it. The selected moused-over) point when a plot tool determines what action is window is displayed. May be carried out when you drag in a displayed as tabbed with other form window. windows. Frame An enclosure around a data box Data box A viewing area in a form., linked or group of boxes containing a to a field in the database associ- label. ated with that form, and displaying data from that field. Framed data A Data box surrounded by a See also: Control box, Picture box labeled frame. box, Profile box, Subform, Text box. Main form Displays data contained in one record of the database. To keep Explorer Displays information on three the display from getting clut- window tabbed (overlapped) windows: tered, tabbed pages may be 1. The Database field hierar- added for less important data. chy. 2. The Queries list that will be Main toolbar Contains icons representing saved with the form. general-purpose menu 3. A “Favorites” list of file commands such as copying, paths. saving, and printing. Click an icon to perform the command. Filter window Displays the filters that modify the BioViz plot. May be Menu bar Contains all the commands displayed as tabbed with other specific to the ChemFinder 11.0 windows. application for manipulating forms, tables, databases, and their contents.

New Record Displays ADD if you are in the indicator process of adding a new record that had not yet been committed to the database.

ChemFinder & BioViz 263 User Guide Screen Element Description Screen Element Description

Administrator Output window Displays Python output. May be Structure box Displays the chemical structure displayed as tabbed with other of the current record. windows. Structure Displays the chemical structure Picture box Displays a graphic. Picture window of the selected (or moused- boxes may be either Fixed, that over) point when a plot window is, they remain the same for all is displayed. May be displayed as records in the database, and are tabbed with other windows. linked to a particular graphic file, or associated with a picture Subform Displays relational information Field, in which case there could from a different database, or a be a different graphic in each different data table within the record. same database.

Profile box New in ChemFinder 11.0. Table header Displays the name of a field. Displays Compound Profiles. Double-clicking on a table header sorts on that field. Query indicator Displays QRY if you are in the process of entering a search Text box Displays text. Text boxes are query. Fixed (text fields are displayed in text data boxes) and may be Read-only indi- Displays READ if the database is formatted in the Box Properties cator read-only and cannot be modi- dialog box. fied. Text Format Used to format text in Text and Record toolbar Contains icons for commands toolbar Memo fields. in the Record menu. Click an icon to perform the command. Title bar Contains the name of the application or document as a Search toolbar Contains icons for commands window title. Also, the title bar in the Search menu. Click an can be dragged to move a icon to perform the command. window.

Status bar Displays information about the Total database Displays the total number of current state of the ChemFinder size records in the current table. 11.0 application.

264 The ChemFinder 11.0 toolbars • Database Wizard—activates the Database Wizard to connect a database to a form. ChemFinder 11.0 uses several toolbars to create and manipulate the ChemFinder 11.0 form and the Form toolbar database records it displays. Toolbars are normally The Form Toolbar contains the tools you need to docked at the top and left side of the UI, but they create objects on a form. Use it to create a new can be “torn off ” and placed anywhere on the form, or to add an object to an existing form. screen for your convenience. Which toolbars are visible is set on the View>Toolbars submenu. You Selection Checkbox Control Box can also use the Toolbars submenu to customize the tool FramePicture Subform toolbars. A description of toolbar customization is beyond the scope of this manual. (See Microsoft help for information on customizing toolbars.) Main toolbar Data Text Profile The Main Toolbar contains the standard tools you Box Framed Box Button Box Grid find in most modern applications: New, Open, and Figure 13.3 The Form Toolbar Save; Cut, Copy, and Paste; Undo and Redo; Print The tools are described in detail in Chapter 4, “Cre- and Help. ating and Editing Forms” on page 51.

New Save Layout Search toolbar

Form Form Paste Redo Print Help Mode The Search Toolbar contains the tools you need to query the database and work with the hitlists that the query produces.

Enter Retrieve Previous Restore Find Query All Query List List Open Cut Copy Undo Switch to Database Form Table Wizard

Figure 13.2 The Main Toolbar In addition, it has three ChemFinder 11.0 tools:

• Layout Mode—switches between Layout Find Find Current Save List Restore (Edit) Mode and View Mode. When the Layout Molecule Previous Mode button is depressed, the Form Toolbar is List visible and an alignment grid appear on the Figure 13.4 The Search Toolbar form. • Switch to Table—switches between Form Record toolbar View and Table View. The Record Toolbar contains the tools you need to browse a database or hitlist. It also has tools for

ChemFinder & BioViz 265 User Guide adding, deleting, and changing records. If you search to find a subset of the entries in the database, then the current list size changes to indi- First Go to Last Undo Omit cate the number of hits in the search. Record Record Record Changes Record

Administrator To the left of these counters are three other indicators that show the general status of the database. The first displays the word READ when you are using a read-only database, such as one that is on a CD-ROM, a read only form file, or if you have se- Previous Next Add a Commit Delete lected Open as read-only on the open file dialog box. Record Record Record Changes Record Figure 13.5 The Record Toolbar Figure 13.7 Status bar, read-only database Text format toolbar The second indicator displays the word ADD when The Text Format Toolbar contains standard text you are entering a new record. formatting tools that you can use when entering or editing information in data and text fields. It is grayed out (not available) when you are not working Figure 13.8 Status bar in add mode in a data or text field. Some options will be grayed The third displays QRY when you are entering a out if the field type does not permit them. query. Font Bold Italic Underline Color Alignment

Figure 13.9 Status bar in query mode

Point Size Subscript Superscript Bullets To hide or show the Status Bar: Figure 13.6 The Text Toolbar Select or deselect the View>Status Bar menu command. The status bar While you move among records, counters in the UI improvements in ChemFinder lower right corner of the ChemFinder 11.0 window change to indicate the current record, the current 11.0 list size, and the total size of the database. The lower left corner of the window displays help for menu Style button for text and frame boxes items and other information. The Box Properties dialog now makes the Style but- When you first open a form, the current list size ton available for frames and plain text labels. This equals the total database size. The total database button opens the Box Style dialog box, where you size changes only when you add or delete records. can set frame type, printability, and other display

266 characteristics. For users of earlier version of ChemFinder 11.0

UI improvements in ChemFinder 11.0 10 Create tabbed windows to save space. Drag a dock- able window over an existing docked window until you see the outline of a tab at the bottom.

: Figure 13.10 Box Styles dialog box 1. Drag Read-only structure box option The Box Style dialog offers a checkbox Box is read- only. Previously this applied only to text and numeric data boxes. In ChemFinder 11.0, it also applies to structure boxes. If you mark a structure box read- only, the structure cannot be edited except in query mode. 2. Tab outline appears Automatic frame label updates The label of a framed box is now updated if you change the field it displays. 3. Final result Themes ChemFinder 11.0offers themes to let you customize the UI style according to your preference. Op- tions include WinXP, Office 2003, Office 2007, and Whidbey. See “ChemFinder 11.0 opening options” Figure 13.11 Creating a tabbed window on page 425 for more information. Find and replace Resizable dialog boxes You can find-and-replace strings in both text and The Box Properties, Plot Properties, Data Import memo fields, either across all records in the current and Data Export dialog boxes, and the script editor, recordset, or in the current record. In either case, are now resizable, allowing you to see more in text find-and-replace is limited to the selected field. windows, tree controls, and so forth. The position To find text: and size is remembered during the current Chem- Finder 11.0 session. 1. Right-click in a text or memo field. 2. Select Find or Replace.

ChemFinder & BioViz 267 User Guide A dialog box appears where you can enter text opens by doing the following: and set the search parameters. 1. Click the File>Preferences menu command. : 2. In the Preferences dialog box, click the General Administrator tab. 3. Select or deselect Show startup dialog. If you choose to hide the ChemFinder 11.0 dialog box, ChemFinder 11.0 will open a new blank form by default when you open the application. To open the ChemFinder 11.0 dialog box when the preference is set to hide: Figure 13.12 Find and replace Click the File>New menu command. Opening ChemFinder 11.0 Using ChemFinder 11.0 with In default mode, ChemFinder 11.0 opens with the databases ChemFinder 11.0 dialog box. The ChemFinder 11.0 dialog box enables you to perform the following ChemFinder 11.0 comes with the Microsoft Jet da- tasks: tabase engine. ChemFinder 11.0 maintains its own table of chemical information—structure, formula, From the New tab: and molecular weight—and relies on Jet to create a • Blank Form—Open a blank form to create database system for managing the rest of the data. your own form. The data created by Jet is stored in an MS Access • Database Connection—Open a blank form database file (MDB file). If you have MS Access in- and connect it to a database. You can create the stalled on your computer, you can use it to work form manually or choose to create it automati- with the relational part of the database. cally. For more information, see “Connecting a You can use ChemFinder 11.0 to add chemical Database to a Form” on page 27. structures to a database you have already developed. • The Database Wizard—Guides you through If your database was developed in Microsoft Ac- the process of setting up a form with a database cess, you can open it directly in ChemFinder 11.0. connection. With ChemFinder 11.0 Ultra, you can use the ChemFinder 11.0/Oracle Cartridge to manage all From the Existing tab chemical and relational data directly in Oracle, with- • Browse to an existing form in your file system. out using DAO or ODBC. From the Recent tab The database model • Open a form on the recently-used file list. A database is a collection of information. In Chem- You can choose whether or not the ChemFinder Finder 11.0 the information is organized into in- 11.0 dialog box is displayed when ChemFinder 11.0 creasing levels of complexity. At the simplest level is the data item itself, for example a molecular

268 weight value. (one for each field) defining a single entry.

Figure 13.13 A data item in the database Figure 13.15 A record in a database At the next level is a field, a group of data items de- A collection of records is a table. A table is defined fining one type of data. Fields are generally set up by a set of fields, and a set of records which grows once and rarely modified. as entries are added. In spreadsheet terminology: • A data item is found in a cell. • A field corresponds to a column. • A record corresponds to a row. • A table corresponds to a worksheet. A database is a storehouse for tables–possibly one, possibly more than one. A database containing only one table is known as a simple (or flat or flat-file) database. Databases containing multiple tables are called re- Figure 13.14 A data field in a database lational. Relational databases are discussed further At the next level is the record, a set of data items in Chapter 9, “Relational Data and Subforms” on page 135. A form displays data from a single table, but may contain subforms that display data from other tables. If the tables have a field in common, then any record retrieved in the form calls up the related records in the subform. Understanding forms and databases It is important to understand the distinction between forms and databases. Databases are where data is actually stored. A form is used only to dis-

ChemFinder & BioViz 269 User Guide play the information stored in the database. No data form. is stored in a form. The form acts like a window, let- ChemFinder 11.0 lets you create more than one ting you select which fields and tables you want to form to access the same database. For example, you

Administrator view. may want to create one sample form for working While no data is stored in forms, some things are with structural data and a more complicated one to saved with a ChemFinder 11.0 form. BioViz plots, include literature or lab data. By switching between database queries (depending on a preference set- forms, you can look at just those fields you want to ting), file paths of linked graphics, and certain set- see. tings you can make in a form are saved with each

270 Chapter 14: ChemFinder 11.0 Tutorials

Overview 3. Select all Cs_Demo.* files. 4. Right-click, then click Copy. The general steps for using ChemFinder 11.0 are: 5. Select the folder you created for the database 1. Create a form. copies. 2. Create or open a database and link it to the form. 6. Right-click then click Paste. 3. Add or manipulate data. You can now experiment with adding, modifying, 4. Perform a search. and deleting data in the copies with no effect on the The tutorials introduce you to ChemFinder 11.0 ba- Cs_Demo database. sic functions. Tutorial 1: Creating forms You may want to use the Quick Reference card while you perform the tutorials. Forms allow you to display your data in a custom- We recommend performing the tutorials in the se- ized format, to browse and search through your da- quence they are presented because each tutorial de- tabase, and to interact with other applications, such velops on and refers to the previous ones. as ChemDraw and Chem3D. You create forms using the Form toolbar shown Sample databases below: The Samples directory located in the \ChemOffice 2006\samples folder contains several small data- Selection Checkbox Control Box tool FramePicture Subform bases, forms, and sample scripts. The Cs_Demo database contains about 300 structures covering a range of structural types. The database contains two tables, both of which are visible using the form Cs_Demo.cfx. This is the form used Data Text Profile in the following tutorials. Demo.cfx is a simpler Box Framed Box Button Box Grid form which displays only the main table of the same Figure 14.1 The Form toolbar database. NOTE: The Form toolbar docks on the left side of the CAUTION: We recommend you make a working copy of the ChemFinder 11.0 window by default, but can be docked any- database before experimenting with it. If you make where or “torn off”, as shown. changes to the data or structures in the database, the For detailed information about each tool, see “Cre- examples in the tutorials may no longer give the ating forms manually” on page 301. documented results. Creating data boxes The following procedure creates a working copy of Data and structures from a database are displayed in the Cs_Demo.cfx database. boxes. You create boxes using the tools in the Form 1. Open Windows Explorer. toolbar. The Form toolbar only appears when you select Layout mode. The Layout Mode tool is on 2. Create a folder for the database copies.

ChemFinder & BioViz 271 User Guide the Main toolbar, so before you begin, look at the 5. Draw two more boxes in the same way. You will View>Toolbars submenu and make sure there are edit them in later steps. check marks next to both Main and Form Edit. Administrator

Figure 14.2 The View>Toolbars submenu Figure 14.4 Step two: three data boxes To create a data box: A Frame, a Framed Box, and a Text Box are different types of boxes and require a label. 1. From the Main toolbar, click New . To draw a Framed Box: A new, blank form appears in the ChemFinder 11.0 window. 1. Click the Framed Box tool and drag diago- 2. If the Form toolbar is not visible, click the Lay- nally to create a framed box. out mode tool . A box labeled Data is created. The Form toolbar appears. 2. Point to the word Data, right-click, and click the 3. Click the Data Box tool . Label... context menu command. The Box Text or Label dialog box appears. 4. In the form window, drag diagonally to create a box.

drag

Figure 14.5 Box Text or Label dialog box 3. In the Box Text or Label dialog box, type 2. release mouse button 1. drag Frame Box and click the OK button. Figure 14.3 Creating a data box

272 The label appears above the Framed Box. The label appears above the box.

Figure 14.6 Creating a label for a data box Figure 14.9 Creating a framed box To place a picture in your form: TIP: You can change the font of the label from the Box tab of the Properties dialog box. Just click the button 1. Click the Picture tool and drag in the form. labeled Font. The Open dialog box appears. 4. Click the Frame tool . 2. Browse to a graphic file, then click the Open but- TIP: The Frame tool is useful if you want to draw a ton. frame around two or more data boxes. NOTE: ChemFinder 11.0 supports EMF, WMF, BMP, GIF, JPG, PNG, and TIF formats. 5. Place the pointer at the corner of the upper right data box and drag to create a border around the The picture appears in the area you dragged in group of three data boxes. the form.

drag

Figure 14.7 Dragging a frame around a data box The Enter the Label dialog box appears.

Figure 14.10 Form with a picture Editing data boxes Edit the data boxes using the Selection tool: Figure 14.8 Enter the label dialog box 6. In the Enter the Label dialog box, type Frame 1. Click the Selection tool . and click the OK button. 2. Select the upper left box by clicking anywhere in it.

ChemFinder & BioViz 273 User Guide A selected data box is designated by four black Select a box, point within the selection, and drag squares at its corners. the box. Administrator

Figure 14.11 A selected box 3. Click an empty space in the form with the Selec- tion tool to deselect the box. Figure 14.13 Repositioning a box by dragging To select multiple boxes: If you select multiple boxes, dragging the center of Press the Shift key and click in each box. a selected boxes moves all of them at once. TIP: You can also select multiple boxes by dragging. To edit with the Clipboard: You can select all the boxes on the form by choosing 1. Select a box. Select All from the Edit menu. 2. Try each of the following menu commands: The frame and the box work as one object when • Edit>Cut you select, move, resize, or delete. To separate them • Edit>Paste into two objects: • Edit>Undo 1. Click inside the Framed box to select it. • Edit>Redo 2. Click the Edit>Bring to Front menu command. NOTE: Undo and Redo work over multiple levels. You can To resize a box: use Undo and Redo repeatedly to reverse multi-step operations. Select a single box, and resize it by dragging a side or corner. Deleting data boxes To delete a data box:, do one of the following: • Select a box and press the Delete or Backspace key. • Click the Edit>Cut menu command. cursor display when dragging To clear the entire form: Click the Edit>Select All menu command, then press the Backspace key to remove the contents Figure 14.12 Resizing a box of the form. To reposition a box:

274 Creating and saving a form The Box Properties dialog box appears with the Database tab displayed. To create and save a new form: 1. Draw the form shown below, using the Framed box tool. You will use this form in the following Tutorials.

Name Structure Formula

Figure 14.15 Box Properties dialog box

NOTE: Figure 14.14 Tutorial 1 target form The “Data Source” option is only available in Layout mode. Make sure the Layout mode toggle 2. Click the File>Save As menu command. button is depressed before performing this step. 3. In the Save As dialog box, save the form as tut1.cfx in the directory of your choice. 4. Click the Open Database button. File>Close 4. Click the menu command. NOTE: The Open and Create Database buttons work with ChemFinder 11.0 databases only. To access Tutorial 2: Opening a database data in other types of databases, use the Attach Table or After you create a form, you can use it to connect the Oracle button (if available). For more information to a database that actually stores information. In about data sources, see “Attaching tables from other this tutorial, you use the form you saved as applications” on page 330. “tut1.cfx” in the previous tutorial to access and retrieve information from an existing database. The Open dialog box appears. Connecting a database to a form To connect a database to your form: 1. Click the File>Open menu command. The Open dialog box appears. 2. Select tut1.cfx and click the Open button. The form you created in the previous tutorial appears, but all of its fields are blank You can use this form to display the demonstration database. 3. Right-click the Structure box and click the Data Source... context menu command. Figure 14.16 Open dialog box

ChemFinder & BioViz 275 User Guide 5. Select CS_demo.mdb and click the Open button. contents of the Structure field for the first The database opens, and the Box Properties record in the CS_Demo database. dialog box appears displaying the Database tab.

Administrator 6. Select a table. A list of the tables in the database and the fields in each table are shown. The field you select determines what type of data appears in the box you selected in step 3.

Figure 14.18 Form displaying a structure To assign fields to the other data boxes: 1. Right-click in the Name box and click the Mol- name context menu command.

Figure 14.17 Database tables in the Box Properties dialog box Assigning fields to data boxes To display structures from the CS_Demo database in a Structure box on your form: From the list of fields in the Box Properties dialog box select Structure, then click the OK but- Figure 14.19 Molname context menu ton. NOTE: Once you have opened a database and table, The Structure field is linked to the Structure the shortcut menu displays the fields in the database. box. In the Structure data box, you can see the The Molname field in the database is linked to the Name box, and the data item for the first record appears in the Name box. 2. Right-click in the Formula box and click the For- mula context menu command.

276 3. Right-click in the ID box and click the MOL_ID The name of the database appears in the Prop- context menu command. erties box.

Database name

Figure 14.20 Form with fields assigned to data boxes 4. Click the File>Save As menu command. Figure 14.21 Database name as it appears in the Form Properties dialog box 5. In the Save As dialog box, save the form as tut2.cfx in the directory of your choice. ChemFinder 11.0 creates one data table 6. Click the File>Close menu command. (MolTable) containing four fields: Structure, Formula, MolWeight, and MOL_ID. Congratulations! You have created your own cus- 5. Click the Field tab. tomized form for viewing the CS_Demo database. You are now going to add two new fields to the Tutorial 3: Creating your own data table. 6. Click the Create Field button. database The Create Field dialog box appears. In this tutorial you will create a new database using the automatic form generation technique. 1. Open a new blank form. 2. Right-click in the form and click the Data Source... context menu. command. The Form Properties dialog box appears with the Database tab displayed. 3. Click the Create Database button. The Save As dialog box appears. Figure 14.22 Create Field dialog box 4. Type mydb and click the Save button. 7. Type MolName in the text box, change the width to 254, and click the OK button. NOTE: The maximum number of characters you can enter in any text field is 254 characters. If you want a text field to contain more than 254 characters, choose Memo/Rich Text from the Type drop-down list.

ChemFinder & BioViz 277 User Guide 8. Click the Create Field button again. Type Boiling The Mydb form is generated. Point in the text box, change the type to Double, and click the OK button.

Administrator NOTE: Use the field type Double to create a field containing real numbers (such as -123.7 and 43.242).

The data table tree display should reflect your changes immediately.

Figure 14.25 Generated form Check the field assignments in the data boxes. Figure 14.23 The Data Tree display 1. Right-click in the structure data box. 9. Click the Form tab. There should be a check next to Structure indicating that the Structure field is linked to the structure data box. 2. Right-click in the Boiling Point data box. There should be a check next to Boiling Point. TIP: You can edit the form to suit your purposes. Notice in the next section that the form has been rearranged to save Generate form checkbox space. Style button Adding records Now that you created new fields and assigned them to data boxes, you can add data to your database. Figure 14.24 Form Properties dialog box This tutorial was written to demonstrate use of the 10.Click the checkbox next to Generate form. Click ChemDraw Control (the default structure mode). the Style button. In the Form Generation dialog Before you begin to add structures, you might want box, make sure the checkbox for Structure in upper to check if ChemFinder 11.0 is set appropriately. left of form is checked. To check the current setting: 11.Click the OK button in the Form Generation 1. Right-click in the Structure data box, and click dialog box and again in the Properties dialog the Properties... context menu command. box. 2. In the Box Style section of the Box Properties dialog box, select ChemDraw style. When ChemDraw style is selected, ChemFinder 11.0 defaults to the ChemDraw control. This allows you to edit structures directly in the Structure data box in ChemFinder 11.0. Chem-

278 Finder 11.0 style opens ChemDraw in its own size of your database is indicated in the Status Bar. window for editing. Now you are ready to begin adding records to your database. Figure 14.27 Form with one record entered 1. Deselect the Layout tool to hide the Form tool- Enter two more records: bar. 1. Click the Record>Add New Record menu com- 2. Double-click in the Structure box. mand. The ChemDraw control appears. 2. Add a record for n-Pentane (shown below), with bp = 36.1. TIP: Even if your default is ChemDraw style, you can open ChemDraw by right-clicking in the structure box and selecting Edit in ChemDraw. Figure 14.28 Pentane structure drawing 3. Select the benzene tool, and draw benzene. 3. Repeat step 1 and then add a record for Cyclo- hexane (shown below), with a bp = 80.7.

C6H6

78.1118

Figure 14.29 Cyclohexane structure drawing

NOTE: After you have two or more records in your database, you can commit changes by moving to a Figure 14.26 Adding a structure with the ChemDraw different record using the Record tools. toolbar 4. Click somewhere outside the Structure data box 4. Click the File>Save menu command. to enter the structure in the data box. NOTE: Choosing Save saves any changes made to The benzene molecule appears in the Structure your form. Clicking Commit Changes saves the data Data box on the form. ChemFinder 11.0 calcu- into your database. lates the molecular formula, and assigns an ID number of 1. 5. Click the MolName box and type Benzene. Tutorial 4: Searching a database 6. Click the Boiling Point box and type 80.1. NOTE: The following examples require you to search the 7. Click the Record>Commit Changes menu com- entire database. This is the default search, unless the Over mand to commit your new record. Current List command is activated on the Search menu. Please take a moment to make sure this command is NOT You entered the first record in your database. The activated before beginning this tutorial. ChemFinder 11.0 helps you organize and find in-

ChemFinder & BioViz 279 User Guide formation. One way to find information is to 2. Navigate to the...\ChemOffice 2008 \ Chem- browse through the database one record at a time, Finder 11.0\samples folder. (Normally, this is in like turning the pages in a book. This is a good way C:\Program files\.)

Administrator to see some of the information available. However, because databases can be very big, browsing is often inefficient. Searching a database is like using the index of a book. With an index, you can quickly focus on the few pages you are interested in. When you search a database, you find only those few records that have the information you look for. After you have this smaller collection (a hit list), you can then browse it much more efficiently than you could the whole database. ChemFinder 11.0 performs the following types of searches: Figure 14.30 The ChemFinder 11.0 samples directory • Text and structure searches, demonstrated in 3. In the Samples directory, select CS_demo.cfx Tutorial 4. and click the Open button. • Reaction searches, demonstrated in Tutorial 5. The CS_Demo database opens in ChemFinder In this tutorial, you will learn how to search sub- 11.0. structures and text in the CS_Demo Database. This database is included with ChemFinder 11.0 as a sample database of approximately 300 organic and inorganic compounds. Opening the demo database To open the CS_Demo database: 1. Start ChemFinder 11.0 and click the Existing tab on the Open dialog box. If ChemFinder 11.0 is already running, click Figure 14.31 The CS Demo database the File>New menu command to open the dia- Before you begin searching, open the Explorer win- log box, or access CS_Demo directly from the Favorites tab of the Explorer Window.

280 dow, if it is not already open. search and then a name search. 1. Click the View>Explorer Window menu command. Formula searching To find compounds in the CS_demo database with six carbons and one or two nitrogen atoms: 1. Click the Search>Enter Query menu command. The form is cleared so that you can enter a new query. 2. Click in the Formula box and type C6N1-2. NOTE: This entry specifies a molecular formula having six carbon atoms and one or two nitrogen atoms.

3. Press the Enter key. The Status Bar indicates that 12 hits were retrieved from the 285 records in the database.

Figure 14.34 Status bar displaying hitlist information Figure 14.32 Selecting Explorer on the View menu The Queries tree in the Explorer window now dis- The Explorer Window appears. plays one query as a “child” of the full list. Queries are saved with the form and can be reviewed at any time. For more information on queries in the Ex- plorer window, see “Managing queries” on page 364 There are three methods for browsing the hits: • In the Form View—Use the Record menu commands or toolbar to navigate through records. • In the Data Table View—Browse the table to view the records. Figure 14.33 CS Demo form with Explorer window • In the Continuous Forms View—view multi- 2. Click the Queries tab, and you are ready to start ple records in their own forms. your first search. To toggle between the different views, click the TIP: The default, set in the Preferences dialog box, is to View>Switch Views menu command or the Ctrl+W save all queries listed in the Queries tree. If you don’t want to keyboard shortcut. save a particular query, delete it before closing the form. To browse the hit list, use the Record menu com- Text searching In this exercise, you perform a molecular formula

ChemFinder & BioViz 281 User Guide mands or their keyboard shortcut equivalents. You can sort the records for a specific field in Table View. To sort records in Table view by the MolWeight

Administrator field: Double-click on the MolWeight table header. The molecular weight field is sorted in increasing order.

Figure 14.35 Switch Views on the View menu NOTE: As you change records, counters in the Status bar indicate the current record, the current list size, and the total size of the database. Figure 14.37 Selecting a field in the Table View To view the database in a table that shows the To change the column widths of your table: records in a list, do one of the following: Position the pointer over a table header divider • click the View>Data Table>In Current Window and drag to the width you want. menu command. • Click the Switch to Table tool. •Type Ctrl+T. NOTE: The Switch to Table tool is a toggle. Selecting it again will return you to the Form view. Pointer The Table view appears and displays all the records of the current list (in this case, the 12 records that were hit by the search) in a table.

Figure 14.38 Changing a field display width To use continuous forms to browse your records: Click the View>Continuous Forms menu command.

Figure 14.36 Displaying the Table View

282 The Continuous Forms view appears. By 2. Click the Search>Enter Query menu command. default, the Continuous Forms view shows the same form as the Form view. TIP: Although the Tutorials describe the use of the Search menu, you may find using the Search toolbar more convenient. The icons on the toolbar match those you have already seen on the Search menu. Clicking the Find icon is equivalent to pressing the Enter key when you are ready to begin your search. See Chapter 18, “” on page 345 for information on more advanced use of the Search toolbar.

The form is cleared so that you can enter a Figure 14.39 Continuous Forms view new query. Adjust the height of any form by dragging the bar 3. Click the Molecule Name box, and type benz*. divider on the left to view the forms clearly. 4. Press the Enter key. To return to the Form view click the View>Form You get 12 hits with names starting with View menu command. “benz”. To retrieve all the records in your database double- 5. Click the View>Data Table>In Current Window click Full List in the Explorer window. menu command. The Table view appears. Browse to verify that the molecular names are correct. Full List NOTE: Notice that this search gave you “benzene” but not “bromobenzene.” The query you entered above is an “anchored substring” and only gives you strings starting with the indicated substring. For more information on how to specify text searches, see “Text searches” on page 345. Numerical searching To search in the CS_Demo Database for compounds with molecular weights between 90 and 100: Figure 14.40 Viewing queries in the Explorer window 1. Switch to the Form View, if you are not already Name searching in it. To find all compounds in the CS_Demo Database 2. Click the Search>Enter Query menu command. with molecular names starting with “benz:” The form is cleared so that you can enter a new query. 1. Switch to the Form View, if you are not already in it. The Form view appears.

ChemFinder & BioViz 283 User Guide 3. Click in the Molecular Weight box and type A blue box is displayed around the Structure 90-100. box and the ChemDraw Control appears. 3. Draw benzene. Administrator

90-100

Figure 14.41 Entering a MW query 4. Press the Enter key. You get 11 hits with molecular weights between 90 and 100. Figure 14.44 Structural query for benzene substructure To set the correct options for a substructure search: 1. Select the Search>Substructure menu option, if it is Figure 14.42 Hitlist information for the MW query not already selected. 5. Click the View>Data Table>In Current Window 2. Deselect the Search>Similarity menu option, if it menu command. is selected. The Table view appears. Browse to verify that The Search menu should appear as follows: the molecular weights are correct. NOTE: A molecular weight query is a decimal value or range. The precision of the search depends on the number of significant digits entered. For more information on molecular weight searching, see “Numeric searches” on page 346. Substructure searching To enter a query and search for a substructure: 1. Click the Search>Enter Query menu command. The form is cleared to allow you to enter your search terms. The status indicator in the status bar is changed to remind you that you are in Figure 14.45 Search menu setting for substructure query mode and the color of the form may searching change 3. Click the Search>Find menu command. ChemFinder 11.0 begins searching. The Figure 14.43 Status bar before a query progress of the search is indicated by counters in the status bar at the bottom of the window. 2. Double-click in the Structure box.

284 When the search is complete, the number of hits is You get 8 hits from the 285 records in the displayed in the Current List Size window of the database. Status Bar, and the form displays the first hit. In a substructure search, the matched portion of each molecule is highlighted in red. Figure 14.47 Status bar results of combined query 6. Click the View>Data Table>In Current Window menu command. Figure 14.46 Status bar results for benzene substructure The Table view appears. Browse to verify that search the molecular weights are correct. NOTE: You can also set search preferences on the Search Congratulations! You have completed the tutorial tab of the Preferences dialog box. For more information, see on searching a database using ChemFinder 11.0. Chapter 25, “” on page 423 You may now close the CS_Demo database. In this search you get 122 hits of structures that contain an aromatic six-membered ring. The list Tutorial 5: Reaction queries you can browse is limited to the hits found in the In addition to helping you organize information search. about individual substances, ChemFinder 11.0 also NOTE: If a search gets no hits, an alert appears and you allows you to store and search chemical reactions. are returned to the query mode with the query on display. There are many ways to search reactions, depending Combined searching on what sort of information you are interested in. In this set of exercises, you learn some general In some cases, you may want to combine structure methods to search for different parts of reactions searching with text searching to find a specific class using a sample from the ISICCR database. This da- of compounds. For example, you may want to find tabase is included with ChemFinder 11.0 as a sam- all compounds in the database that have a benzene ple database of approximately 250 reactions substructure and that have a molecular weight extracted from the ISI’s ChemPrep database of greater than 400. Current Chemical Reactions. To perform a combined search: Opening a specific database 1. Click the Search>Enter Query menu command. The form is cleared so that you can enter a To open the ISICCR database: new query. 1. Click the File>Open menu command. 2. Double-click in the Structure box. The Open dialog box appears. The ChemDraw Control appears. 2. In the Samples directory, select Isiccr.cfx, and 3. Draw benzene. click the Open button. 4. Click the Molecular Weight box and type >400. NOTE: The ISICCR.cfx form is formatted for a large 5. Press the Enter key. screen (1024 X 768). If you have a smaller screen, open ISICCRsm.cfx for a simpler form.

ChemFinder & BioViz 285 User Guide The ISICCR database opens in ChemFinder The Search menu should appear as follows: 11.0. Administrator

Figure 14.48 The ISICCR form Searching for reactants

Searching for reactants is useful if you have a Figure 14.50 Search menu setting for substructure known starting material and you are interested in searching learning more about what substances it can pro- 6. Click the Search>Find menu command. duce. ChemFinder 11.0 begins searching. The For example, to search for Grignard reactions, or progress of the search is indicated by counters reactants: in the status bar at the bottom of the window. 1. Click the Search>Enter Query menu command. When the search is complete, the number of hits is The form clears. displayed in the Current List Size window of the 2. Double-click in the Structure box. Status Bar, and the form displays the first hit. In a substructure search, the matched portion of each The ChemDraw Control appears. molecule is highlighted in red. 3. Draw the following: You get 3 hits—reactions in which an alkyl magnesium halide is consumed. Browse the list of three hits as in previous tutorials. Figure 14.49 Entering a reactant in a query Searching for products This structure represents a carbon atom bonded to a magnesium atom, which is In the next exercise, you search for information on bonded to any type of halogen. The arrow at a particular reaction product. Searching for prod- the right indicates that you are looking for this ucts of reactions is very common in syntheses, substructure as a reactant. where you know what you are aiming for but you do not know how to produce it. In this example, we 4. Select the Search>Substructure menu option, if it is look for reactions that close a ring alpha to a carbo- not already selected. nyl. 5. Deselect the Search>Similarity menu option, if it is selected. To perform a reaction product search: 1. Click the Search>Enter Query menu command. The form is cleared so that you can enter a new query. 2. Double-click on the Structure data box.

286 The ChemDraw Control appears. For example, to search for reactions that reduce a 3. Draw the following: carbonyl to an alcohol: 1. Click the Search>Enter Query menu command. The form is cleared. 2. Double-click in the Structure box. 3. Draw the following: Figure 14.51 Entering a product in a query O OH 4. Switch to either selection tool (Lasso or Mar- quee) and select the single bond next to the double bond. Figure 14.54 A reaction type query structure 5. Right-click, point to Topology, and choose Ring. 4. Press the Enter key. 6. Select the remaining single bond. Browse through the 23 hits. Each of the reac- 7. Right-click, then click the Topology>Ring context tions found shows the transformation of a car- menu command. Right-click again, then click the bon-oxygen double bond to a carbon-oxygen Reaction Center>Make/Break menu command. single bond. Your structure should now look like this: This hit list includes reductions of aldehydes, acids, and ketones. Search over list Figure 14.52 Product query with topology and reaction center indicators In this example, you start with the previous list and search again to get only ketone reduction reactions. The arrow at the left indicates that you are looking for this substructure as a product. To search over a list: 8. Press the Enter key. 1. If you are not continuing directly from the last You get 3 hits containing a product with a car- example, double-click the previous query in the bonyl ring that was formed during the course Query Tree to make sure it is the active hitlist. of the reaction. 2. Click the Search>Over Current List from the menu.

O 3. Double-click in the Structure box. OH HO HO O 4. Draw the following: H H

H Cl Cl H Cl

O O Figure 14.53 One of the product query hits Searching by reaction type In many cases, you have some idea of both your Figure 14.55 Adding a reactant search starting materials and your products, but are looking for some information on how to get from one a. Using a Selection tool, right-click on the to the other. double bond and set Reaction Center bond properties to Change.

ChemFinder & BioViz 287 User Guide b. Using the Text tool, select one of the carbon Congratulations! You have completed the tutorial atoms. Type [NOT O,H] (all uppercase, with on searching for reactions using ChemFinder brackets as indicated) and press the Enter 11.0.You may now close the ISICCR database.

Administrator key to replace it. c. Still using the Text tool, select the label, Tutorial 6:BioViz quickstart right-click and choose Repeat Last Label. BioViz is the ChemFinder visualization facility. d. Double-click on the other carbon atom to With BioViz, you can create graphical representa- reproduce the label. The structure now tions of any numerical data in your database and looks like this: store the charts with the form (CFW file). You can plot data for the full database or for a domain or query lists. You can filter the plots using multiple filters, and perform simple statistical analysis on the data. Creating a BioViz chart Figure 14.56 Modified reactant query BioViz charts are created from the View>BioViz You have specified a search for ketones by add- Plots submenu, or from the data field context ing the restriction that the atoms adjacent to menu. Existing plots can be displayed (when not the carbon must not be oxygen atoms or visible) or removed from the form with the View hydrogen atoms. You also specified that the menu. You may create a plot based on any numeri- double bond had to change, not be broken. cal field in the database. The following options are available: 5. Press the Enter key. You get 13 hits. Each reaction shows the • Line plots with one or two variables reduction of a ketone to an alcohol. In the • Scatter plots with one or two variables Queries Tree, this search is shown as a “child” • Histograms (X-axis variable only). of the first query. Single variable plots A single variable plot displays a Y-coordinate variable vs. the record number.

Figure 14.57 A child search in the queries tree TIP: If you plan to do several searches over a hitlist, use the Set Domain to Current List command rather than Search Over Current List. Setting a domain eliminates the need to keep restoring the original hitlist.

288 To create a single variable plot: first 500 points in the dataset will be plotted. On most computers, this will take no more than a few seconds. To 1. Point to BioViz Plots on the View menu: plot a larger dataset, reset this value as necessary.

6. Click the OK button. The Plot appears in a new window:

Figure 14.58 Creating a BioViz chart 2. Select New to bring up the BioViz Plot Proper- Figure 14.60 A single variable plot. ties dialog box: 7. Click the Notes tab to view addition information. For example, points will not be plotted if they are missing Y values. This is reported in the Notes Histogram plots A histogram plot is a variation of a single variable plot, where the X-coordinate is the variable value, and the Y-coordinate shows the count in each histogram cell. To create a Histogram plot: point limit BioViz Plots>New Figure 14.59 Plot properties 1. Click on the View menu. 2. Click the One Variable radio button in the Dimen- 3. Click the One Variable option in the Dimension sion box of the BioViz Plot Properties dialog box. box. The X-coordinate is grayed out and the Analy- 3. Click the Histogram radio button in the Style box. sis tab is not displayed. 4. Click either the Number or Size radio button in 4. Select any numerical field from the drop-down the Bins box and enter a value (optional). menu for the Y-coordinate. • Number sets how many bars will appear in 5. Enter a name for the plot (optional). the plot TIP: Note the Point Limit field on the lower right side • Size sets the number of data points per bar. of the Properties dialog box in Figure 14.59 above. 5. Select any numerical field from the drop-down Plotting a large dataset can be very slow. As a safely menu for the X-coordinate. precaution, the default is set to 500, meaning only the 6. Enter a name for the plot (optional).

ChemFinder & BioViz 289 User Guide 7. Click the OK button. You may select the axes in either order. Once you have selected a field for an axis, it is displayed in the context menu. Administrator

x-axis (previously Figure 14.61 Histogram plot selected) The high and low values of each bar are displayed under the plot. Figure 14.63 Two-variable selection with the context Two-variable plots menu If you want to change the axis assigned to a field, se- In two variable plots, you choose both the X and lect Reset X,Y and start over. the Y coordinates. To create a two-variable plot: Working with plots 1. Click BioViz Plots>New on the View menu. Three optional windows facilitate working with 2. Click the Two Variable option in the Dimension BioViz plots: Structure, Filter, and Details. box. • Structure — displays structures of data points 3. Select fields for both the X and Y axes. as you mouse over them; used when the form is 4. Click the Scatter plot option in the Style box. not visible or is displaying a different record. 5. Enter a name for the plot (optional). • Details — displays data for selected fields, 6. Click the OK button. either from the database or from child tables, as you mouse over data points; used when the form is not visible or is displaying a different record. • Filters — displays filter bars for those fields being used to modify the plot. Activate these windows from the View menu now. To save space, you may then drag them over one an- Figure 14.62 Two-variable plot

290 other to create a toggled window. different field.

Figure 14.65 Applying a filter. In this example, the Y-axis values have been trimmed to remove values above 850.

Figure 14.64 Using tabbed windows TIP: In order to see some of the features described below, you will need to “tile” the windows to view the form and the plot simultaneously. Figure 14.66 MW for SD>0 Filters In this example, the plot is filtered to only show Filters can be used in two different ways: compounds with a positive SD above a control. • Filter a plotted variable to reduce its range Autoscale • Filter on other variables to add other dimen- When you filter a plot, you may want to expand the sions to the plot. scale to better display the remaining points. If you To activate filters, click the View>Filter Window select Autoscale on the BioViz context menu, the menu command or use the context menu (Right- scale will readjust automatically every time you ad- click menu) for plots. When the filter window just a filter. Autoscale is a toggle that remains in ef- opens, Right-click in it to select or deselect fields. fect until you cancel it. There is no limit to the number of filters that can be Alternately, you can make all of your filter adjust- applied to a plot. ments without changing the scale, then select Res- NOTE: Filters act on all active plots, not just the one dis- cale to All Points on the BioViz context menu. played. Zoom Two examples show how a plot can be modified using filters. In the first, Figure 14.60 is filtered on the The BioViz zoom feature is a toggle activated from field plotted (MW). In the second, it is filtered by a the BioViz context menu. To expand a portion of a BioViz plot:

ChemFinder & BioViz 291 User Guide 7. Select Zoom on Drag on the BioViz context You may repeat zoom, that is, zoom in on an area menu. in an already expanded scale. If you have performed A check mark appears next to the command multiple zooms, the Zoom button acts as an Undo

Administrator when it is selected. To deselect, click the com- control, reversing one step at a time. mand again. Statistical analysis 8. Drag over a section of the plot. When you release the mouse button, the scale You can perform statistical analyses on plots using expands to show the points selected. the Analysis tab on the BioViz Plot Properties dialog box. The tab is available only for two-variable plots. 1. Selecting an area The following statistical parameters may be calcu- to enlarge lated: • Minima and maxima of the X or Y variable. 2. Enlarged area • Mean or median of the X or Y variable. • Standard deviation of the X or Y variable. When you select curve fitting, the R squared value also becomes available for display. The calculated values are displayed below the plot. You may also display a linear, quadratic, or cubic least-squares fit of the data points, with or without a confidence interval of one to three standard devi- Zoom ations. buttons

Figure 14.67 Using the Zoom Feature While the initial view is the area you selected, you may use the scroll bars to view any part of the plot at the expanded scale. Clicking either the X or Y Zoom Button will return that axis to the original scale, while leaving the other axis at the expanded Figure 14.68 Plot with statistical analysis scale. Clicking Unzoom on the BioViz context menu The following table describes how to perform vari- will restore the original scale to both axes simultaneously.

292 ous functions in BioViz. if you want to... then result See which data point corre- navigate to the record using the The data point is highlighted. sponds to a particular ChemFinder Record Toolbar. record... View the structure or data mouse over the data point. The Structure window displays the struc- values of a data point... ture for the data point; the Details window displays the values of selected fields. (The current record in the form does not change.) Select a database record click on a data point. The form displays the matching data from the plot... record. Display plotted variable(s) select (or create) the query. The plot displays the current query. for a query... Create a query from the On the BioViz context menu: The selected points become a new query. plot... 1. If a check mark appears next to Zoom on Drag, click to deselect it. 2. Drag over the points of interest to select them. 3. Click Selection to List on the context menu. Prevent a plot from check the Lock option in the BioViz The plot is locked to a given dataset. changing when you select Plot Properties dialog box. Note that filters will be locked as well. queries or change variables... Expand the plot to view Select Zoom on Drag on the BioViz Dragging over a section of the plot individual data points... context menu. enlarges it, rather than selecting the points. Change the color of the data In the Queries control, select Change The data points are displayed in the color points... Color on the Queries context menu. you select. Note that you cannot change the color of the Full List, only of daughter lists.

Table 1 : BioViz Features

ChemFinder & BioViz 293 User Guide if you want to... then result Plot multiple datasets With the Full List selected, click Color A check mark appears in the box next to

Administrator (overlay)... on Plot on the Queries context menu the query name, and the data points are for each query you want to overlay. displayed in the color assigned to the Alternately, click the query or the query. colored box next to it.

Table 1 : BioViz Features

Tutorial 7: Working with 2. Make some space on the right side of the form by rearranging the data boxes and making them subforms smaller. Subforms allow you to display relational data. If you have a database containing two or more data tables, and these data tables share a common, linking field, then you can display data from both tables. When- ever the value of the linking field changes in the main form, the subform only displays those records from its table which have the same value in the linking field. You can also use subforms to display data from different databases.

In this tutorial, you open the CS_Demo database Figure 14.69 MyDb form rearranged to make space for a and display the MolTable in the main form. Then subform. you display the Synonyms table of the CS_Demo database in a subform. By defining the MOL_ID 3. Click the Subform tool . field as the linking field, you display the two sets of 4. In the form, drag to create a large subform. data relationally. TIP: If you cannot make room on the right side of your Creating a subform form, you can put the subform at the bottom of the form. To create a subform: 1. Open your ChemFinder 11.0 form tut1.cfx. Opening this form connects you to the CS_Demo.mdb database.

294 When you release the mouse button the Sub- form. Clicking in either form activates it. form Properties dialog box appears. To test this: 1. Click anywhere outside the subform box, and browse your database using the Record tools. As each molecule record of the MolTable is displayed, the subform shows the first matching ID from the Synonyms table. 2. Click inside the subform box. Now when you browse, you are browsing only the entries in the subform. To display all of the synonyms:

Figure 14.70 The Subform Properties dialog box 1. Toggle out of Layout mode . 5. Click the Form tab, then select Synonyms from the 2. Double-click in the subform box to switch to hierarchical tree display. Table view. 6. Click the Generate form checkbox, then click the Style button. 7. Select the Plain form, deselect all of the fields to be included except Synonym, and click the OK button. You are returned to the Subform Properties dialog box. 8. Click the Subform tab. 9. SYN_ID already appears as the default in the Link to SYNONYMS field section. Using the drop- Figure 14.71 Form with subform down menu, choose MOL_ID for the Link from Save and close the file: MOLTABLE field. 1. Click the File>Save menu command. 10.Click the OK button. 2. Click the File>Close menu command. You have just selected the data source for your subform and linked it to the main form. Congratulations! You have completed the Chem- The MOL_ID field links the main form and sub- Finder 11.0 Tutorials.

ChemFinder & BioViz 295 User Guide Administrator

296 Chapter 15: Creating and Editing Forms

Overview existing form” on page 317). The first step in designing a form is selecting the da- You use forms to interact with information in a database and deciding which fields to include. tabase. A ChemFinder 11.0 form is composed of data boxes for viewing or modifying data items, Selecting a database such as structures, numbers, text, or pictures. A form can also contain subforms for relational ac- A ChemFinder 11.0 form does not store data di- cess to different data tables and different databases. rectly, but is simply the window through which you You can create a form in the following ways: look at data. When creating a form, you need to specify the source of the data to display. A form dis- • Automatically, using the Form Generator dia- plays data from a single table in a database. To spec- log box. ify the data source for a form, you must open or • Manually, using the Form tools. create a database, and then select a table. • With the Database Tree. If you want to view data from more than one table, The example below shows a form displaying a sin- you must create a form for each table. Typically, you gle record of information from a database. create a main form for one main table and a subform for each other table. For more information, see Chapter 20, “” on page 383. You can connect a database to the form before creating boxes, or any time after. If the form is already connected to a database, you can change the database or the data source. If the form has boxes with fields connected to them, then the boxes automatically connect to fields of the same name in the new- Figure 15.1 Form, showing a single record. ly-opened database. Creating a form consists of creating a layout (see Opening an existing chemical database “Creating forms manually” on page 301), and setting box properties (see “Setting box properties” on To open a database to associate with a form: page 307), tabs (see “Creating and editing tabs” on 1. Right-click on the form and click the Data page 305), and security (see “Securing forms” on Source... context menu command. page 317). The Form Properties dialog box appears. You can edit your form at any time (see “Editing forms” on page 314 and “Changing the layout of an 2. Click the Open Database... button.

ChemFinder & BioViz 297 User Guide The Open dialog box appears. You can use the Box Properties dialog box, as described in “Setting box properties” on page 307. To choose the data box to display: Administrator 1. Right-click in a box or frame, then click the Field... context menu command. The Field properties appears. 2. From the data source tree, select the field to display.

Figure 15.2 The Open dialog box 3. In the Open dialog box, choose a database with an MDB file extension, then click the Open button. The Form Properties dialog box reappears with a data source tree displayed. The CS_Demo database is shown below. Figure 15.4 Selecting a field in the database tree 3. Click the OK button. The field data is displayed in the box. If you use this method with a framed box, the box label will remain unchanged. If you want to use the field name as the box label, you can do it in one step as follows: 1. Right-click in a framed box. 2. Select the field name from the list at the bottom of the right-click menu. The frame receives the field name and the data Figure 15.3 The CS Demo database Form properties is displayed in the box. 4. Click the OK button. The database is associated with the form. Selecting the data to display You indicated the source of the data to display on the form, but the form is still blank. To see the data, you need to indicate what data to show in each box. Figure 15.5 Selecting a field name from the context menu.

298 Opening a secured MS Access database 5. Select the permissions you want to assign for that object type to each user or group. To open a secured Microsoft Access database in 6. Click the Apply button. ChemFinder 11.0, you need to set the appropriate permissions in MS Access. 7. When you have finished assigning permissions, click the OK button. NOTE: Check this infoIf your database was created in MS Access 97 (as, for example, were some of the ChemFinder 8. Open the database in ChemFinder 11.0. 11.0 sample databases), and you are using a newer version Creating a database of Access, you must convert the database before you can edit it. These instructions assume a database created in You can create a new, empty database and associate Access 2002. Other versions may differ slightly as to options it with a form. and procedures. To create a database: To set the permissions: 1. Open an existing form, or create a new one. 1. Open the desired database in MS Access. 2. Right-click in the form and click the Properties... 2. Click the Tools>Security>User and Group Permis- context menu command. sions menu command. The Box Properties dialog box appears. 3. Click the Box Properties Database tab, then click the Create Database... button. The Save As dialog box appears. 4. In the File Name box, type a name for your database, and then click the Save button. A data source tree appears, containing the database and its tables and fields. 5. Click the OK button. The Box Properties dialog box closes. Creating forms automatically Use the Form Generation dialog box to create a form or change the layout of an existing form. In the dialog box, you choose the form style and prop- Figure 15.6 User and Group Permissions dialog box erties from pre-defined options. 3. Select the Users or Groups radio button to To begin creating a new form: assign permissions to individuals or groups. 1. Right-click on a blank area of the current form 4. Select an Object Type from the drop-down and click the Data Source... context menu com- menu. mand. The Form Properties dialog box appears.

ChemFinder & BioViz 299 User Guide 2. In the Form Properties dialog box, select the 6. Select the Form style you want: Form tab. If you want the boxes Then, in the Form

Administrator to style section, click

be surrounded by a Framed. frame

be labeled above Titled.

Generate form checkbox and Style button be labeled to the left Labeled.

Figure 15.7 Generating a form automatically not be labeled Plain. Generate form 3. Select the check box, then click the Table 15.1 Form style options Style... button. 7. Use the thumb wheel arrows to select the num- The Form Generation dialog box appears. In ber of columns, from one to four, in the Col- the left panel, all of the Fields are selected by umns: list. default. 8. Use the Grid size: drop-down menu to choose the size and spacing of the boxes and grid as follows:

If you want the boxes to Then, for Grid be Size, choose

larger and spaced further Large. apart

Figure 15.8 The Form Generation dialog box medium, relative to the Medium. 4. Deselect those fields in the Choose fields to be Large and Small settings included section that you want to exclude from the form. smaller and spaced closer Small. 5. To have a Structure box in the upper left corner together of the form, select the Structure in upper left of form checkbox. Table 16 Grid size options If you do not select this option, the boxes are 9. Click the OK button in the Form Generation dia- generated in the order they appear in the list. log box. Your form settings are saved.

300 10.Click the OK button in the Form Properties dia- 2. Choose the directory in which you want to save log box. the form, type a filename, and click the Save but- A warning dialog box appears allowing you to ton. create a new form or replace the existing form. ChemFinder 11.0 saves the form with a CFX Click No to create a new form, Yes to replace extension the existing form. Creating forms manually You create a form and define it by using the Form tools to create objects and the Box Properties dialog box to set the form properties.

Figure 15.9 New form warning box. Creating a new form The generated form appears in the window. To create a new form, do one of the following: Saving a form • Click the File>New menu command. In most non-database applications—including • Click the New File icon on the Main ChemDraw and Chem3D—you edit data on the Toolbar. screen, but your changes are not made permanent A blank form, Form1, appears. until you click the File>Save menu command, or type Ctrl+S. In database programs such as ChemFinder 11.0, your changes are automatically and permanently saved to the database when you switch records. This is “committing” the changes. You then have the opportunity to revert to the original data by clicking the Record>Undo Changes menu command. Figure 15.10 Blank form The File>Save menu command refers only to changes made on the form itself, such as the position of boxes. Using the form tools Choosing the File>Save menu command has no ef- You must use the Form Tools toolbar to design a fect on changes you make to data stored in the da- form. Box creation commands are not available tabase. Saving a form also saves subforms and from the menu. changes that you make to subforms. To display the Form tools, do one of the following: After you create a form, you can save it. When you retrieve the saved form, it automatically opens a • Click the Layout icon on the Main toolbar. connection to the database defined in the forms. • Select the View>Toolbars>Form menu option. To save a form: 1. Click the File>Save menu command. To save the form under a new file name, use File>Save As. The Save dialog box appears.

ChemFinder & BioViz 301 User Guide The Form toolbar appears providing tools for tabase. Data boxes do not have labels, but you can you to create and edit a form. label them by adding a Frame or Plain Text. You can also use the Data Box to display static data not from Selection Checkbox Control Box

Administrator a database. tool FramePicture Subform To draw a Data Box:

1. Click the Data Box tool . 2. On the form, drag diagonally to create a box.

Data Text Profile Box Framed Box Button Box Grid Figure 15.11 The Form toolbar Using the grid In a new form, the snap grid is turned on by default. This grid helps you align boxes on the form. Turn- ing on the grid forces objects to snap to the grid as they are drawn. Figure 15.12 A data box created in a form. To toggle the grid on or off, do one of the follow- To specify what type of data is displayed in the box, ing: see “Setting box properties” on page 307. If the form already has a database open, you can right- • Click the Grid tool on the Form toolbar. click in the data box, select Field... and choose from • Select/deselect the View>Grid menu option. a list of the available fields. NOTE: You can change the grid spacing using the Prefer- Creating frames ences dialog box. See “Setting preferences” on page 423. The Frame tool allows you to create an enclosure Creating boxes with a label surrounding a data box or group of boxes. When you draw a new frame, you are auto- A ChemFinder 11.0 form is composed of a collec- matically prompted for a text label to be attached to tion of boxes that display data from the associated it. database, or other information. Each box displays one data item of the current record. To create a data To create a frame: box, use one of the tools on the Form toolbar. 1. Click the Frame tool . NOTE: The Form toolbar is not visible unless the Layout 2. On the form, drag diagonally to create a frame. button is selected. A framed box appears with the label Data. To The Data Box displays a data item or structure. Use change the label: it to display any data from a database, including text, 3. Right-click on the label and choose Label from numbers, dates, molecules, reactions, or pictures. It the drop-down menu. is the only box that allows you to edit data in the da-

302 The Enter the label dialog box appears. The framed data box is labeled.

Figure 15.13 The Enter the Label dialog box Figure 15.14 Creating a framed data box 4. Type the label you want to attach to the frame. To edit the label of a framed data box: 5. Click the OK button. 1. Select the frame by carefully right-clicking near A fixed label appears on the frame. the edge of the framed box and select Label. To change a label: 2. In the Enter Box Label dialog box, type the new label. The label does not have to match the name 1. Right-click on the edge of a frame and click the of the field displayed in the box. Label... context menu command. OK 2. Enter the new label in the text box. 3. Click the button. Another way to change a frame’s label is in the Box When you create a data box and frame with the Properties dialog. For more information, see “Set- Framed Box tool, these two items are connected. ting box properties” on page 307. To manipulate them separately: You can use a frame to show “live” data from the Select the Framed box, then click the Edit>Bring database. If a frame is connected to a database field, to Front menu command. it is updated automatically as you browse or search. Automatic labels For example, you might place a frame around a structure field, where the label on the frame repre- You can let ChemFinder 11.0 automatically label sents the name of the current structure. The label your framed box with the name of the field from changes every time the structure does. You must the data tree. use Box Properties to set up a live data connection To automatically label a Framed Box: for a frame. Right-click inside the data box and select the Creating boxes with frames field from the drop down list. The data appears in the data box and the frame The Framed Box tool allows you to create a data label changes to match the field name. box and a frame simultaneously. You name the frame in the Enter the Label dialog box. You cannot automatically label a frame that was created separately from a data box. To create a framed data box: Non-data boxes 1. Click the Framed Box tool . 2. On the form, drag to create a box. Boxes are not only used to display data. The Form toolbar contains two tools, Plain text and Picture, to 3. In the Enter the Label dialog box, type the label create static displays (though they may also used to you want to attach to the frame, and click the OK display data) and three others with special func- button. tions.

ChemFinder & BioViz 303 User Guide Adding plain text 3. Click the OK button. The Plain Text tool allows you to display text with- The contents of the field are displayed in plain out a box or a frame. You can use it to place a static text. Administrator label on the form, but, like a data box, you can also Adding pictures use it to display live data if desired. The Picture tool allows you to create a Picture Box To use the Plain Text tool: to display a bitmap (BMP, GIF, etc.) or Windows metafile (WMF, EMF) picture. It can display a static 1. Click the Plain Text tool . file, or a live one stored in a picture column of a da- 2. On the form, drag to create an area to specify tabase. where the text will appear. To create a static picture: The Enter the Text dialog box appears. 1. Click the Picture tool . 2. On the form, drag to create an area for the picture to occupy. The Open dialog appears. 3. In the Open dialog box, select the file you want Figure 15.15 The Enter the Text dialog box to display, then click the Open button. 3. Type the text you want to display. The picture appears in your form. 4. Click the OK button. NOTE: The file is not actually embedded in the form. Only

its filename is saved with the form. If you move or rename the Figure 15.16 Creating text on a form file, the form will not display the corresponding picture. How- To change the font or color of the text, select it with ever, if you make changes to the picture and keep its filename the Form toolbar Selection tool . Use the text the same, the picture in the form will be updated. formatting toolbar to customize the text. To create a Picture box linked to a field. To use plain text to display data: You must have a picture field in the database. See “Creating fields” on page 331 for more 1. With the Select tool, right-click on the text and information. click the Properties... context menu command. The Box Properties dialog box appears with 1. Click the Picture tool . the Box tab displayed. 2. On the form, drag to create an area for the pic- 2. Select a field from the data table. ture to occupy. The Data: text box becomes grayed out, and The Open dialog appears. the Data Source selection switches to Field. 3. Click the Cancel button.

304 A blank box appears in the form. 4. Right-click, and select a Boolean or Integer field 4. Right-click in the box and click the Properties... from the field list to assign to the checkbox. context menu command. Adding a button 5. In the Box Properties dialog box, select the picture field you want to link to the box and click Buttons on the form are used to activate scripts. the OK button. To place a button on a form: The picture field item appears in the box. 1. Write a script using the ChemFinder 11.0 Auto- To read in a picture file or to replace a picture in a mation Language (CAL). Picture Box: 2. Click the Button tool on the Form toolbar. 1. Right-click a picture and click the Read File con- 3. On the form, drag to draw a button. text menu command. The Enter the Label dialog box appears. The Open dialog box appears. 4. Enter a label. The text can be descriptive (“Click 2. In the Open dialog box, select the file you want to browse”) and does not have to correspond to to display in the Picture Data Box, then click the the name of the script. Open button. 5. Click the OK button. The new picture is displayed in the Picture Box. For more information about using a button to run a script, see “Using scripts” on page 435. NOTE: If the Picture box is linked to a Picture field, you must click the Commit changes tool to save the Adding a subform picture in the database. The Subform tool is used to create a subform box to display data from a related data table. See “Rela- To save a file from a Picture Data Box: tional Data and Subforms” on page 383 for more 1. Right-click on the Picture Box and click the Save information File context menu command. Adding a profile 2. In the Save As dialog box, type a file name, then click the Save button. The Profile box tool creates a profile box on a form. Compound profiles are a new feature in The picture is saved. ChemFinder 11.0. See “Compound Profiles” on Adding a checkbox page 389 form more information. The Checkbox tool allows you to add checkboxes Adding a control to your form. A Checkbox can be assigned to either The Control box tool is used to embed an ActiveX a Boolean or an Integer field. control in a form. You can use this to display a cal- To add a checkbox: endar, spreadsheet, chart, spectrum, picture, web 1. Click the Checkbox tool. link, and so forth. See “Embedding ActiveX con- 2. On the form, drag an area large enough for the trols” on page 429 for more information. text next to the checkbox. Creating and editing tabs The Enter the label dialog box appears. If you have a large number of fields in a database, 3. Type in the text and click the OK button. you can access information more easily, and make

ChemFinder & BioViz 305 User Guide the form less cluttered, by using tabs to divide a To view the Database Tree (if it is not visible): long form into smaller parts contained on separate 1. Select the View>Explorer Window menu option. tabs. 2. Click the Database tab.

Administrator To create tabs on a form: To use the Database Tree to build a form: Right-click an empty part of a form and click the Add Tab context menu command. 1. Open a new form. Two tabs appear in the lower left corner of the 2. Right-click in the form, and click the Data form. Clicking on the second tab will present Source... context menu command. you with a new empty form. 3. Click the Open Database... button on the Database tab. 4. Browse to a database, and click the Open button. 5. Click the OK button in the Form Properties dia- Tabs log box. The Database Tree displays the database.

Figure 15.17 Creating a tabbed form To rename a tab: 1. Right-click the tab and click the Rename Tab context menu command. The Tab Name dialog box appears. 2. Type a name for the tab and click the OK button. The new name appears on the tab. Figure 15.18 Creating a form with the database tree To remove a tab: 6. Double-click the Structure field in the Database Right-click the tab and click the Delete Tab context Tree. menu command. A structure box appears in the upper left of the The tab is removed. form. Creating forms with the database tree The Database Tree is the same familiar tree as in the Database Properties dialog, showing the tables (or views) and columns of the currently-open database. When you open or activate a form or subform, or change databases, the tree updates to display the Figure 15.19 Structure box created from the database tree current database, and expands to show the columns 7. Continue double-clicking the other fields. of the currently-selected table. 8. Use the Selection tool to move the data boxes to where you want them in the form.

306 Setting box properties • Plain Text–displays alphanumeric data. Text data can be displayed in multiple lines. (Use Use the Box Properties dialog box to set Chem- Ctrl+Enter to start a new line.) You set the Finder 11.0 form attributes, including: data source, field size when you create the field, up to a display type, font, and box style. maximum of 254 characters. To open the Box Properties dialog box: • Picture–displays Windows metafile data. Pic- Right-click on a data box and click the Proper- tures are scaled to fit within picture boxes, with ties... context menu command. fixed height to width ratios. The Box Properties dialog box appears. • Formula–displays any kind of text but num- NOTE: The “Properties” option is only available in Lay- bers are subscripted. Formulas are presented in out mode. modified Hill order, as follows: If a substance contains both carbon and hydrogen, the carbons are listed first, followed by the hydrogen atoms, followed by other elements alphabetically by element symbol. If a substance contains carbon, the carbons are listed first, followed by other elements alphabetically by element symbol. Otherwise, all elements are listed alphabetically by element symbol. • Button–used to create buttons to actuate scripts. Buttons display button labels. • Rich Text—displays styled data in multiple lines. (Use Ctrl+Enter to start a new line.) You Figure 15.20 The Box Properties dialog box can format the text with the Text Format tool- Setting data box styles bar. If the data in a field contains rich text, markup characters are displayed. Use the Box Properties dialog box to change the • Structure (ChemDraw style)–displays chemical style of a data box on a form. For example, you can structures or reactions. Reactions are laid out change a data box to a frame or picture. for best fit with the box and the layout may The Box Style menu only shows applicable styles change if the box is reshaped. The box defaults for each field. For example, you cannot show a real to using the ChemDraw Control to create and number in a Picture. edit structures, but you can reset the prefer- For information about field types, see “Creating ence. For more information, see “Setting pref- fields” on page 331. erences” on page 423. Choose from the following styles: • Structure (ChemFinder style)–as above, but defaults to opening ChemDraw to create and • Data Box—displays alphanumeric data. Can edit structures. display multiple lines of data. • Structure (Chem3D style)–as above, but • Frame—displays alphanumeric data. Can dis- defaults to display 3D structures. play a single line of data.

ChemFinder & BioViz 307 User Guide To set the box style: To choose how to view structures: 1. Right-click in the data box you want to change 1. Right-click in a structure data box and choose and click the Properties... context menu com- Properties.... Administrator mand. The Box Properties dialog box appears. The Box Properties dialog box appears. 2. On the Box tab, in the Box Style section, select 2. Choose the box style from the Box Style drop- the structure format to view from the menu: down menu. 3. Click the OK button. If you want to Then choose Viewing structures You can display structures in a structure box in edit in the Structure Structure (ChemDraw three styles: box using the Chem- style). Draw Control •ChemFinder • ChemDraw edit in ChemDraw Structure (ChemFinder • Chem3D style). In ChemFinder style, the ChemDraw application opens when you want to edit structures or create a insert 3D images Structure (Chem3D query. (This mode of operation was used in all ear- style). lier versions of ChemFinder 11.0.) In ChemDraw style, you edit directly in the structure Table 17 Structure box format options box using the ChemDraw Control. (This mode of Viewing structures in Chem3D format operation was introduced in ChemFinder 8.) Unlike the ChemDraw and ChemFinder 11.0 styles, The Chem3D style is a display-only format that al- Chem3D style is view only. You cannot edit the lows you to rotate and analyze structures within a structures in Chem3D style. ChemFinder 11.0 structure window. See the To activate the Chem3D Control: Chem3D User’s Manual for information on using the Chem3D Control. Double click in the 3D Structure Box. The ChemDraw format displays more graphically- Click outside the box to deactivate the control. rich drawings than the ChemFinder 11.0 format. To rotate the structure: However, ChemFinder 11.0 does not use all of the ChemDraw drawing features when searching. For ex- Drag in any direction in the box. ample, textual annotations are ignored, and Unlike in Chem3D, you do not have pure R-group tables are not recognized. Certain graph- (locked) X- or Y- axis rotation, but you can ics, such as rectangles and orbitals, are not trans- approximate them by dragging horizontally or ferred., nor does ChemFinder 11.0 consider their vertically. chemical implications. The Chem3D Control displays different context menus, depending on whether you Right-click while pointing to the model or while pointing elsewhere in the Structure Box. Either can be used to change the display mode.

308 To change the display, method one: 3. Select a display mode from the View>Model Dis- play>Display Mode submenu 1. Double click in the 3D Structure Box to activate the Chem3D display. 2. Point to an atom or bond in the model and Right-click. 3. Select a display mode from the Display Mode submenu.

Figure 15.22 Chem3D display –changing display mode, method two Figure 15.21 Chem3D display –changing display mode, For more information on the Chem3D Control, see method one the Chem3D User’s Manual. can this reference be Method two: fixed - made live? 1. Double click in the 3D Structure Box to activate Setting fixed and live data the Chem3D display. In the Box Properties dialog box, you can designate 2. Right-click anywhere in the 3D Structure Box, whether the data source is fixed or from a field. but not on the model itself. Fixed data is attached to the form and does not change as you browse. Data from a field is stored in the database and is different for each record. As you browse, the record display updates according to the contents of the field. To specify live data for a data box: 1. In the Box tab, select the field to associate, and then click the Field radio button.

Figure 15.23 Specifying live data

ChemFinder & BioViz 309 User Guide 2. Click the OK button. The Choices tab appears. The box display updates as you change records. To specify fixed data for a data box: Administrator 1. In the Box tab, select the field to associate, and click the Fixed radio button.

Figure 15.24 Specifying fixed data 2. Type a label in the text box. If you choose a structure or picture field, click the browse tool Figure 15.25 Adding a menu to a data box to browse to the file to display. 3. Take the appropriate action: 3. Click the OK button. The box display is fixed. If you want to Then click Adding a data box menu use a list from a data- From table and follow You can add a menu containing a list of choices to base table as the data the instructions at the a data box so you can choose an item from it to ap- box menu bottom of the dialog pear in the data box. box. To add a menu: 1. Right-click on a data box and click the Proper- create your own list Fixed list of choices ties... context menu command. for the data box and follow the The Box Properties dialog box appears. menu instructions at the bottom of the dialog 2. On the Box tab, click the With drop-down choices box. checkbox.

use a list from a data- a. From table. base table and add A list appears. your own items to the b. Click Fixed list data box menu of choices, and edit the list. Table 18 Menu list options 4. Click the OK button to close the dialog box, then click in the data box.

310 A button appears in the lower right corner of The scroll bar appears on the bottom right in the box when you click in the box. the data box.

Figure 15.26 Data box with a button for drop-down menu 5. Click the button to display the menu.

Figure 15.27 Using the drop-down menu Figure 15.28 Data box with scroll bar 6. Select any item on the menu—the text appears Hiding data boxes in the top left corner of the box and the button disappears. You can show or hide boxes when switching be- Click within the data box to make the button tween query and browse mode. For example, you reappear. can hide non-searchable data boxes during query entry, or show only those data boxes that display in- Adding a scroll bars formation useful for query entry. Scroll bars are used to accommodate lengthy data When you are in form layout mode, all boxes are when there is limited space for the data box. visible, regardless of the setting. To add a scroll bar: To hide data boxes: Properties... 1. Right-click a data box and click the Properties... 1. Right-click on the box and click the context menu command context menu command. The box properties dialog box appears. 2. In the Box Style area, select the Hidden in Browse Mode check box or the Hidden in Query Mode 2. In the Box style section, select the With scroll bars check box. checkbox 3. Click the OK button. 3. Click the OK button. 4. Deselect the Layout Mode button to view the results. Customizing text Use the Text Format toolbar to customize text fonts, sizes, styles, colors, and alignment in form boxes. All of the standard text formatting options are available. To display the Text Format toolbar: Select the View>Toolbars>Text Format menu option.

ChemFinder & BioViz 311 User Guide The Text Format toolbar appears. • Currency symbol NOTE: Text copied from a word processor such as • Decimal position Microsoft Word retains its styles when pasted into a Rich • Scientific notation

Administrator Text box. To specify the numeric format: The text format toolbar is active: 1. Right-click in a data box containing numeric data • When you are editing a memo field in a rich and click the Properties... context menu com- text box. In this case, font changes apply only mand. to the current selection within the text. The Box properties dialog box appears. • When you are editing in a regular data (or struc- 2. Click the Format... button. ture) box. Font changes apply to the entire contents of the box. The Numeric Format dialog box appears. • When you are in form edit mode, with the selector tool active, and one or more boxes are selected. Font changes apply to all selected boxes (except frames around data boxes). Customizing fonts All labels on ChemFinder 11.0 objects can be edited to your specifications. You can edit any label’s font, font style, size, and color. To set the font for a label: Figure 15.29 The Numeric Format dialog box 1. Click on the label to select it. 3. Select the appropriate option: 2. Right-click, then click the Properties... context menu command. If you want to display Then click 3. On the Box tab of the Box Properties dialog box, click the Font... button. a varying number of Unformatted. The Font dialog box appears. decimal places

4. Set the text font, style, size, and color. a currency symbol Currency and select The sample area previews the font. the symbol from the 5. Click the OK button to commit the changes. drop-down menu. NOTE: To change the color of the atom labels in the structure box, you must use the Periodic Table. See “Using the the currency symbol Symbol on right when a periodic table” on page 428 to the right of the currency symbol is number selected. Customizing numbers Using the Box Properties dialog box, you can spec- Table 19 Numeric format options ify how numeric data is displayed in forms you can customize the following properties:

312 2. Click the Form tab to display the Form proper- If you want to display Then click ties.

a standard Fixed point and select floating-point value the number of with a selected decimal places. number of decimal places

the numbers Scientific and select displayed in scientific the number of notation decimal places.

Table 19 Numeric format options Figure 15.30 Form properties dialog box An example of the format you select is shown in the Sample area of the dialog box. 3. Take the appropriate action: 4. Click the OK button. The format is applied to the current data box. To set the background Click... color of the... Setting color You can set the following color options: database form the Form Background button. • The form background color • The color of the form in query mode query form the Query Background • The default background for all forms button.

To set the form background and form query colors: Table 20 Background color options 1. Right-click in a data box and click the Properties... The Color dialog box appears. context menu command. The Box Properties dialog box appears.

Figure 15.31 The Color picker dialog box

ChemFinder & BioViz 313 User Guide 4. Select a color. A highlight appears around the object indicat- 5. Click the OK button. ing that it is selected. The Form or Query Background button Administrator changes to reflect the color you choose. Selection Marks To set the default background color:

1. Click the File>Preferences menu command. Figure 15.32 Selection marks on a data box The Preferences Dialog Box appears. To select multiple objects on a form: 2. Click the Color tab. 1. Click the Selection tool on the Form toolbar. 3. On the Color tab, click the Form Background button. 2. Do one of the following: 4. In the Color dialog box, select a color and click • Press the Shift key and click on the multiple the OK button. objects. The color you chose becomes the default form • Drag the Selection tool around the boxes background color. you want to select. To select all the objects in the form: Editing forms Click the Edit>Select All menu command. You can move or resize boxes and other objects on your form with the Selection tool and the items in Moving objects the Edit menu. Use the Selection tool to move data boxes or other Selecting objects on a form objects to a different place on a form. To move objects on a form: Use the Selection tool to choose data boxes and other objects on a form that you want to move, re- 1. Click the Selection tool on the Form toolbar. size, or delete. When the selection tool is active, the Edit menu 2. Select the object to move. commands apply to the boxes themselves. When 3. Drag the object to a different place. the selection tool is not active, the Edit Menu commands apply to the contents of the active data box. NOTE: To move a subform, you must drag the title bar of To select an object on a form: the subform, not its contents. If an object is nearly in the right place, you can Click the Selection tool on the Form toolbar, “nudge” it to get it exactly aligned. , then click an object on the form to select To move an object one pixel at a time: it. 1. Select the object you want to move. 2. Press an arrow key in the direction you want to move the objects. The objects move one pixel in the direction of the arrow key.

314 Resizing objects To remove objects from a form: Use the Selection tool to resize a data box or any 1. Click the Selection tool on the Form toolbar. other object on the form. NOTE: You cannot resize more than one object at a time 2. Select the object you want to delete. or simultaneously resize a box and its frame, unless you create a framed box using the Framed Box tool. For more infor- TIP: Use Shift+click to select multiple objects. mation, see “Creating boxes with frames” on page 303. 3. Do one of the following: To resize objects on a form: • Click the Edit>Clear menu command. 1. Click the Selection tool on the Form toolbar. • Use the Backspace key. The object is removed from the form. 2. Position the pointer over an edge or corner of the object until the pointer is a double-headed Reversing and restoring changes arrow. Use the Main Toolbar icons or the Edit menu to reverse or restore recent changes to a form. To reverse or restore changes: Click the Edit>Undo... menu command to reverse Figure 15.33 Resizing a data box a change., or click the Undo icon 3. Drag in the direction you want to resize. Click the Edit>Redo... menu command to reverse If an object is nearly the right size, you can make a change., or click the Redo icon small adjustments to get it exactly the size you want. NOTE: Undo and Redo work over multiple changes. To resize objects one pixel at a time: Either command can be used repeatedly to reverse multi-step 1. Select the object you want to resize. operations. 2. Place the mouse pointer over an edge or corner Ordering objects of the object until it is a double-headed arrow. 3. Press an arrow key in the direction you want to The Bring to Front and Send to Back commands place resize the object. data boxes in a specific sequence. They have two ef- The edge of the object moves one pixel in the fects: direction of the arrow key. • Select which overlapping data box is on top. Deleting objects • Set the order in which the cursor moves when you press the Tab key. Use the Selection tool to remove data boxes and To put a box on top or bottom: other objects from a form. 1. Click the box to select it. 2. Do one of the following: • Click the Edit>Bring to Front menu command to put it on top, or

ChemFinder & BioViz 315 User Guide • Click the Edit>Send to Back menu command to put it on the bottom If you want to line up Then choose along the The order in which data boxes are created is the or-

Administrator der in which the cursor moves as you press the Tab key. You can set which data box the cursor moves middle of an object in Vertical Center. to first or last. a vertical line To set the cursor to move to a data box first: bottom edge of an Bottom. 1. Select the data box. object 2. Click the Edit>Send to Back menu command. 3. Press the Tab key. left edge of an object Left. The cursor moves to the box you set. To set the cursor to move to a data box last: middle of an object in Horizontal Center. 1. Select the data box. a horizontal line 2. Click the Edit>Bring to Front menu command. The box you set is the last box the cursor right edge of an Right. moves to when you press Tab repeatedly. object Aligning and distributing objects Table 21 Object alignment options The form objects line up according to your You can line up objects relative to each other by choice. aligning them and space objects at an equal distance apart by distributing them. To space objects on a form evenly: NOTE: In framed dialog boxes, the inner data box is 1. Press the Shift key and click the objects to dis- aligned, not the frame. tribute. To line up objects on a form: 2. Use the Edit>Distribute submenu to take the appropriate action: 1. Press the Shift key and click the objects to align. 2. Use the Edit>Align submenu to take the appro- If you want to space Then choose priate action: objects evenly between the If you want to line up Then choose along the outer boxes of the Vertically. form top edge of the first Top. object you place on left and right of the Horizontally. the form form

Table 21 Object alignment options Table 22 Object spacing options The form objects are spaced according to your choice.

316 Changing the layout of an existing form The Form Security dialog box appears. Changing a form layout is the same as automatically creating a new form. When you have created a new form, you can use it to replace the old form or save it as an alternate form. See “Creating forms automatically” on page 299 for details. Securing forms You can control the options available to users of your forms by setting the security options. You can also provide the database connection information used to log on to an MS Access database. Figure 15.34 The Form Security dialog box MS Access provides a security system that allows TIP: The lower left corner of the dialog box indicates the creation and management of usernames and whether security is defined. passwords, and the assignment of permissions to those usernames. MS username password account 3. Type the Username to use for logon in the User- information is stored in the Workgroup Informa- name box. tion file (.mdw, .mda). For more information about The Enable button becomes available. securing an MS Access database, see “Opening a se- 4. Type the Password to use for logon in the Pass- cured MS Access database” on page 299. word box. Setting security options NOTE: Use of a password is optional. To set what ChemFinder 11.0 form options are 5. To enforce Workgroup Security in an MS Access available to users: Workgroup Administrator database you must 1. Right-click in the form you want to secure, and specify a Workgroup Information File. Take the click the Properties... context menu command. appropriate action: The Box Properties Dialog box appears, with NOTE: Enforcing workgroup security is optional. the Form tab displayed. 2. Click the Security... button. If you want to Then NOTE: The Security button does not appear if the security on your form has been set to not allow access to the Security options. enter a work- Type the name of the MS group file name Access Workgroup database in the Workgroup Information File box.

browse for the Click File and select the workgroup file file.

Table 23 Workgroup naming options

ChemFinder & BioViz 317 User Guide The following steps refer to the options in the En- Administrator

318 able/Disable section of the dialog box. the options; take the appropriate action: 1. Click the plus sign (+) next to Database Security to display the options; take the appropriate action: If you want users to... Then select...

If you want users to... then select... open or create data- Open/create database bases be prompted to log on Password to open form with a username pass- create forms Create new forms word to open a form open forms Open other forms use a username pass- Logon to MS Access word to log on to the database edit forms Save changed forms MS Access database (MDB files) change the layout of a Change form layout form be prompted to log on Prompt for database logon to a database with a use all of the above Forms username password options when the form is open Table 25 Forms security options use a username pass- Protect molecule data- 3. Click the plus sign (+) next to Automation to dis- word to open the base play the options; take the appropriate action: molecule database (MST files) If you want users to Then click

be able to access the Security dialog avail- access OLE automa- Allow CAL/OLE Form Security dialog able. tion writing and Automation access box programming NOTE: Must be encounter all of the Database security. checked to enable export above options to Excel

Table 24 Database security options use scripts Can use scripts menu 2. Click the plus sign (+) next to Forms to display edit scripts Edit scripts

use all of the above Automation options

Table 26 Automation security options

ChemFinder & BioViz 319 User Guide 4. Click the plus sign (+) next to Edit to display the options; take the appropriate action: If you want users to Then click

Administrator If you want users to Then click edit and view struc- Edit/view structures in tures in ChemDraw ChemDraw clear forms Clear view structures in View structures in Chem3D Chem3D delete relational and Cut structural data perform all of the Browse above options copy relational and Copy structural data and Table 28 Browsing security options multiple table rows to 6. Click the plus sign (+) next to Search to display the clipboard the options; take the appropriate action:

paste relational and Paste If you want users to Then click structural data from the clipboard submit queries Query database records Perform all of the Cut/copy/paste above functions use current hit list for Search over current list searching Table 27 Editing security options 5. Click the plus sign (+) next to Browse to display search the entire data- Search over full data- the options; take the appropriate action: base base

If you want users to Then click save and manipulate hit Enable hit list tools lists browse databases Browse database records search exact structure Full structure only view data in forms in a View form as table table search substructures Substructure only view data in contin- View in continuous uous view forms view search similar struc- Similarity tures only Table 28 Browsing security options Table 29 Searching security options

320 To complete setting security: If you want users to Then click 1. Click the Enable button. 2. Click the OK button. use all of the above Searching options The options you choose are applied to the form. Table 29 Searching security options Disabling security 7. Click the plus sign (+) next to Update records to display the options; take the appropriate action: To disable security and reset defaults: 1. Right-click in the form and click the Properties... If you want users to be Then click context menu command. able to 2. In the Form tab of the Form Properties dialog box, click the Security... button. update database Update records The Form Security dialog box appears. records 3. In the Form Security dialog box, click the Disable button. add database records Add new records The Validate Security dialog box appears. NOTE: delete database records Delete records This form only appears if you entered a password when you enabled security. See“Setting Table 30 Update security options security options” on page 317 8. To allow users to import data SDFiles or RDFiles select Import data. 9. To allow users to export data, including delimited text files select Export data 10.Click the plus sign (+) next to Print to display the options; take the appropriate action:

If you want users to Then click Figure 15.35 The Validate Security dialog box 4. Enter your password, then click the OK button. print a single record only. Single record Security is disabled and the defaults are reset. “Security Disabled” appears in the lower left Print several records Several records corner of the Form Security dialog box. Overriding security Use print preview mode Print preview In order to edit security options, you must temporarily remove security. In this case, you should use perform all of the above Print the Override option rather than the Disable option. functions

Table 31 Printing security options

ChemFinder & BioViz 321 User Guide To temporarily disable security: 4. Enter your password, then click the OK button. 1. Right-click in the form and click the Properties... You are allowed to edit the security options. context menu command. “Security Overridden” appears in the lower left

Administrator corner of the Form Security dialog box. 2. In the Form tab of the Form Properties dialog box, click the Security... button. 5. When you have completed your changes, click the Override Security button to toggle security The Form Security dialog box appears. back on. 3. In the Form Security dialog box, click the Over- “Security Enabled” appears in the lower left ride Security button. corner of the Form Security dialog box. The Validate Security dialog box appears. NOTE: This form only appears if you entered a password when you enabled security. See“Setting security options” on page 317

322 Chapter 16: Working with Databases

Overview • If the component files (extensions CFX, MDB, LDB, MST, MSI) have read-only attributes. You work with data within ChemFinder 11.0 by en- • If the files are on read-only media, such as tering it into a database, editing it, and interfacing CD-ROM. with ChemDraw and Chem3D. • If you select Read-only in the File Open dialog You can perform all of these functions on data us- box when you open a form or database. ing the commands in the menus, or you can use the buttons in the Record toolbar for most of these When you open a read-only database, the following functions. conditions apply:

Add Commit Omit • READ appears in the status line. Record Changes Record • You can not modify data in text or structure boxes. NOTE: If only the form (CFX) file is set to read-only, READ does not appear on the status line and the database can be modified. Undo Delete Changes Record Multi-user access Figure 16.1 Database functions on the Record toolbar If a database resides on a network, more than one ChemFinder 11.0 user may access it at the same Opening databases time. Each user can view, print, or modify records independently of the others. When you open a database in ChemFinder 11.0, you can access the data in any of three ways: The following table shows how the type of user affects the other users in the group. • Normal access—you can read and write data. • Read-Only access—you can read but not User type Affect on other users write data. The database is write-protected. • Secured access—you must open the database Multiple readers in User actions do not affect with a user name and password. You are subject read-only access each other. to the security restrictions applied to the database. Multiple writers in All users can read and write. NOTE: Versions of ChemFinder 11.0 earlier than 7.0 normal access A user may see another user’s cannot read ChemFinder 11.0 7 or greater .cfw files. Ver- edits. If two users try to edit sions of ChemFinder 11.0 earlier than 11.0 cannot read .cfx the same area at the same files. time, one is alerted that the database is temporarily Read-only access locked. Any of the following conditions determine whether a database opens in read-only mode: Table 16.1Multi-user access

ChemFinder & BioViz 323 User Guide username and password to log on. User type Affect on other users When you open a secured MS Access database from within ChemFinder 11.0, a username, pass-

Administrator One writer, The writer, in normal access, word, and workgroup information file is required. multiple readers is not affected by the readers. Contact your Access Database Administrator for The readers, in read-only this information. access, may see the writer’s To open a secured form: edits. 1. In the Validate Security dialog box, type your Table 16.1Multi-user access username and password, and then click the OK If two people are viewing the same record within a button. database, and one person changes the data in that record, the second person will not see the changes immediately. The changes will be visible when the second user switches to another record, and then back to it. Secured access ChemFinder 11.0 supports the following types of Figure 16.2 The Validate Security dialog box security: If the form you access includes a secured molecule database, the Database Logon dialog box • Form access—ChemFinder 11.0 enforces appears. form access security by requiring a user name and password, which are stored in the form (CFX) file. • Molecule file access—ChemFinder 11.0 enforces molecule file access security by requiring a user name and password, which are stored in the database’s MST file. • Microsoft Jet Relational Database Engine—the database engine that underlies Microsoft Access enforces security. The user Figure 16.3 ChemFinder 11.0 Molecule Database Secu- names and passwords are stored in an MS rity dialog box Access Workgroup Administrator database. 2. Type your Username, Password, and Workgroup Information File name (if applicable), then click For more information on Form access, see “Secur- the OK button. ing forms” on page 317. For more information on MS Access security, see “Opening a secured MS Ac- The form opens. cess database” on page 299. Browsing databases When you open a form or database that has security options applied to it, you are prompted to enter a You can browse a database using the buttons on the

324 Record toolbar. The specified record is displayed. NOTE: Record numbers are temporary, referring only to Go to Record Last Record First Record positions within the current list in its current sort order. For example, if you have done a search that found ten hits, then the only valid record numbers are 1–10. If you want to move to a specific absolute location in a database, you must run a search for a value in a field that identifies that location. Previous Record Next Record The data table Figure 16.4 Browse functions on the Record toolbar To Browse: Sometimes browsing through a data record set is more convenient if the data is presented in tabular • Click First Record to display the first record in format. the database. NOTE: You cannot add or modify records while viewing • Click Previous Record to display the record data in a table. before the currently shown record. To display data in a table: • Click Next Record to display the record after the currently shown record. Click the View>Data Table>In Separate Window menu command (or type Ctrl+T). • Click Last Record to display the last record in the database. A list window containing the fields and records in the form appears. NOTE: The current record number is displayed in the Status Bar.

Go directly to a specific record as follows: 1. Click the Record>Go To Record menu command. The Record Number dialog box appears.

Figure 16.6 Data Table view in a separate window

Figure 16.5 The Record number dialog box To display a particular record in the form: 2. Type the number of the record (within the cur- Click the record’s entry in the list window. rent list) to display, and click the OK button. By default, the fields in the Data Table are displayed in the order in which they were created.

ChemFinder & BioViz 325 User Guide To reorder the columns in the Data Table: 2. Drag to adjust the column width. 1. Click one of the column headers to select the NOTE: To hide the column, right-click and choose column.

Administrator Hide Column from the context menu. Column selection indicator To resize the row heights in the Data Table: 1. Place the cursor on the dividers in the left header. The cursor changes to the icon shown below.

Figure 16.7 Column selection indicator in the Data Table view 2. Drag the header to a new position. The cursor changes to the icon shown below. The new position is indicated with a red vertical line. Figure 16.10 Changing the height of a row 2. Click-drag to adjust the row height.

NOTE: To resize all rows, right-click in a column header and choose Resize Rows to Fit from the context Figure 16.8 Moving a column menu. To resize the column widths in the Data Table: 1. Place the cursor on the dividers in the top R-group tables header. In Data Table display, you can display a substruc- The cursor changes to the icon shown below. ture search as table of R-group substituents. 1. Run a substructure search. NOTE: You cannot prepare a table from a full structure or similarity search.

Figure 16.9 Changing the width of a column

Figure 16.11 Substructure query to set up R-Group table

326 2. Switch to Data Table view. • the other rows are populated with the Rs hit.

Figure 16.12 Table view of query results Figure 16.14 R-Group table 3. Right-click in the Structure column, and click the NOTE: The data in this table is just for display. It is not R-Group Table context menu command. saved with the form. The table will continue to be displayed The following changes occur: when you toggle the Table view until you change the hit list by • the topmost structure is replaced with the running another query or restoring the full list. template – similar to the query you used, but To sort an R-Group Table: with Rs attached at all positions which found 1. Right-click the header of any R column (R1, R2, substituents. etc.). 2. Click the Sort Column>[command] context menu command. The options are: • Ascending • Descending •Multiple Ascending and Descending sort by the molecular Figure 16.13 R-Group query and template weight. Multiple opens a dialog box that lets you sort by another parameter or group of parameters. • new columns are generated for all the Rs. To set up a multiple sort: 1. Select fields in the order in which you want them to apply. 2. Right-click selected fields to change the sort order (ascending, descending) or to remove an unwanted parameter. You can cut and paste R-group cells containing either structures or text using the clipboard.

ChemFinder & BioViz 327 User Guide R-Group plots Creating a database Once you’ve generated an R-group table, you can Instead of opening an existing database, you may then plot the various substituent groups against any want to create a new, empty one. Administrator other plotable field. To create a new database using the automatic form 1. With the table view still displayed, click the generation technique, see “Tutorial 3: Creating your View>BioViz Plots>New... menu command. own database” on page 277. The following proce- 2. On the General tab, click the X or Y variable to dure results in a simple database with one table for display the drop-down menu. storing structures. The R-Group positions are now included in To create a database: the menus, and may be used like any other 1. Right-click in the form and click the Properties... numerical field to create a plot. context menu command. 2. On the Database tab, click the Create Database button. The Save As dialog box appears. 3. Choose the directory to which you want to save the database. 4. Specify a name for the database, and click Save. ChemFinder 11.0 creates the database containing one table (called MolTable) with four fields:

• Structure

Figure 16.15 Setting up an R-Group plot. • Formula

• Molecular weight

• Mol_ID

The Mol_ID field corresponds to a column in the table where a numeric ID is automatically entered as each structure is registered. The other fields represent information stored in the structural portion of the database, linked to the assigned ID. The Formula and Molecular weight data are au- Figure 16.16 R-Group 2 vs. Molecular Weight tomatically calculated from a structure. These inter- Note the R-Groups along the X-axis in nal fields cannot be edited or deleted. Figure 16.16, corresponding to the values in the R2 After creating a database, you can create fields for column of the table display (see Figure 16.14). The storing other types of data. It is not necessary to structure on the upper right corner of the plot is the create the entire set of fields before working with template. the database. You may add more fields later.

328 Creating tables The Create Table dialog box appears. There is no limit to the number of tables a database can contain. You may want multiple tables in a database in order to manage relational data, or simply to organize different collections of information in the same place. A table must contain at least one column. When you create a new table, ChemFinder 11.0 creates a Figure 16.18 Create table dialog box numeric column called ID. You can use this column to store integer data, or delete it and replace it with 4. Type a name for the new table, then click the OK your own columns. button. The table appears in the Data Source tree. Table names must: • Begin with a letter • Not contain punctuation characters • Not be the same as a table already on display To create a new, empty table: 1. Right-click in the form and click the Properties... context menu command. The Box Properties dialog box appears. 2. Click the Table tab. The Table tab appears: Figure 16.19 Adding a new table to the Data source tree Deleting tables To delete a table from the database: 1. Right-click in the form and click the Properties... context menu command. The Box Properties dialog box appears. 2. Click the Table tab. The Table tab appears: 3. In the data source tree, select the table to delete. Figure 16.17 Table tab on the Box Properties dialog box 4. Click the Delete Table... button. A dialog box appears giving you the option of 3. Click the Create Table... button. completing the deletion or cancelling. 5. Click Yes to delete the table.

ChemFinder & BioViz 329 User Guide The table and all data it contains are immedi- The Attach Table dialog box appears. ately deleted from the database.

CAUTION: Administrator You cannot undo a deleted table. Before you delete a table, create a backup copy of the database to prevent accidental loss of data. For more information, see “Backing up databases” on page 334.

Attaching tables from other applications You can use ChemFinder 11.0 to add chemical structures to a database you have already developed. If your database was developed in Microsoft Ac- Figure 16.20 Attach table dialog box cess, you can open it directly in ChemFinder 11.0. 3. Click the Open MS Access Database... button. ChemFinder 11.0 can also work with data from oth- The Open dialog box appears. er file-based databases such as dBASE and xBase NOTE: The list of file types available in the Attach clones, but in this case you must open or create a Table Open dialog varies from one computer to another. ChemFinder 11.0 database and attach the table to The files for which you have drivers installed shown. For link to tables in the data source. After you attach a example, if Paradox is not installed, you may not have table, it appears and functions as if it were part of Paradox drivers on your system or in the drop-down list. your local ChemFinder 11.0 database. The procedure you use depends on whether the ta- If the database type you wish to access is not on the list, bles you want to attach are from a file-based (Ac- it may not be a file-based system, and you need to cess, FoxPro, dBASE) or non file-based (Oracle) connect using ODBC. For detailed instructions, see database system. “Attaching files from a non file-based database” on Attaching files from a file-based database page 330. To attach a file-based database table: 4. Choose the database to access, then click the OK button. 1. Right-click in the form and click the Properties... context menu command. 5. In the tree diagram, click the table you want to attach, then click the OK button. 2. Click the Table tab, then click the Attach Table button. The newly-attached table appears in the tree diagram in the Form Properties dialog box. 6. Click the Form Properties OK button. Attaching files from a non file-based database If the database you want to attach is not file-based, such as Oracle, you can attach it using Microsoft's Open Database Connectivity (ODBC).

330 To attach a non-file-based database table: The newly-attached table appears in the tree diagram in the Form Properties dialog box. 1. Right-click in the form and click the Properties... context menu command. 7. Click the Form Properties OK button. 2. Click the Table tab, then click the Attach Table The source of the data to display on the form is in- button. dicated, but the form is still blank. To access the da- The Attach Table dialog box appears. ta, you need to draw some data boxes, and indicate 3. Click the Open Oracle/ODBC Data Source button. what data to show in each of those boxes. The Select Data Source dialog box appears. Creating fields Whether you created a new database or are working in an existing one, you can add or remove fields in the selected table. You can choose from the following types of fields: Text field—Allows you to enter text such as names, comments, and references. A text field is fixed in length, and requires that you choose a maximum length (“width”) for any data item to be stored in the field. If you enter a width of 50, then you can’t store any item with more than 50 characters in that field. Figure 16.21 Select Data Source dialog box You can specify widths of text fields as large as 254 4. From the Machine Data Source tab, select the characters. If this is insufficient, you need to create ODBC data source to access, then click the OK a Memo/Rich Text field instead. button. Because the text field width cannot be modified af- NOTE: The ODBC data source dialog box shows all ter a field is created, it is often wise to err on the side data sources known to ODBC, including ChemFinder of caution and make it longer than you need initially. 11.0, Access, and other file-based data sources. If you On the other hand, larger field widths also create attempt to open one of these through the ODBC dialog, larger files and slower search times. you get an error message. File-based data sources must NOTE: Non-ASCII characters will not display correctly be opened using Open Database, as described above. in a data table text field.

If the ODBC data source dialog does not show the Integer field—Used for whole numbers such database you seek, you may need to create a new data as ID's. All integers in ChemFinder 11.0 are long, so source. You can do this using the New button. For can accommodate billions of values (232 of them). details, click the Help button in the ODBC dialog box. Double field—Used for real numbers such as 5. If you are prompted for a user name and pass- physical constants and unit prices. Real numbers in word, enter it. If you don't know what name and ChemFinder 11.0 are double-precision. In Chem- password to use, see your System Administrator. Finder 11.0 11, double fields can serve as ID fields. 6. In the tree diagram, click the table you want to Picture field—Allows you to store a bitmap file attach, then click the OK button. (BMP,GIF, JPEG, PNG, or TIFF) or Windows

ChemFinder & BioViz 331 User Guide metafile (WMF, EMF), such as a spectrum or exper- Date field—Allows you to store dates. The imental setup, as a data item in a database. dates are displayed according to the settings in the A Picture box on a form may be used to display a Windows Regional Settings control panel. Administrator static picture attached to the form, such as a logo, Structure field—Consists of four fields: a nu- or it may be used to show pictures stored in the da- meric ID stored in the relational database, plus tabase which change as you move from record to three fields (Structure, Formula, MolWeight) that record. If you import a database containing pictures take data from the ChemFinder 11.0 structure data- (type Long Binary or BLOB) they will be interpret- base files. ed as pictures and the form generator will create a picture box for it. Boolean—Used with checkboxes. When searching Boolean fields, you can only search for Memo/Rich Text field—Used to display text. ON. This is because ChemFinder 11.0 automatical- Memo fields can be of any length. Because memo ly clears all fields when activating the Queries form. fields are less structured, searching them can be slower than searching a text field. Additionally, You can create more than one set of structure fields memo fields cannot be sorted. in a table. Each is assigned a unique set of names, and each refers to its own ID column in the table, To search for text: although all structural data is taken from the same 1. Right-click in a memo or plain text field. structure database files. 2. Select the Find Text context menu command. To create a field: The Find Text dialog box appears. 1. Right-click in the form and click the Proper- ties...context menu command. The Box Properties dialog box appears. 2. Click the Field tab. The Field properties appear.

Figure 16.22 Find text dialog box 3. Enter the text and the match conditions. 4. Click either the Forward or Backward button to search. 5. To search for the next occurrence, do one of the following: • Click the Find Next context menu command. •Use the F3 key. Memo fields can store Styled Text. For more infor- Figure 16.23 Field properties dialog box mation, see “Styled text” on page 341. 3. Click the Create Field button.

332 The Create Field dialog box appears. 5. When prompted whether you want to delete the selected field, click the OK button to delete or click Cancel to leave it unmodified.

CAUTION: When you delete a field, all data contained in the field is also deleted. You are not warned explicitly about this.

Adding multiple structures Figure 16.24 Create Field dialog box You can include more than one structure on the 4. In the Name box, type a name. same form by creating multiple structure columns 5. In the Type box, choose a data type from the in a table. Each structure column you create repre- drop-down menu. sents four types of data: 6. For text fields only, type a width (number of • The structure displayed as a diagram. characters) in the Width box, or use the thumb • The Molecule ID, which connects the structure wheels to select a value. to a record in a relational table. 7. Click the OK button. • The formula derived from the structure. The name of the new field appears in the data source tree. • The molecular weight derived from the structure. Deleting fields To create multiple structure columns in a table: Just as you can create any field and assign it to a data 1. Click the File>Database... menu command. box at any time, you can modify the database by de- The Form Properties dialog box appears. leting fields from the selected table. 2. Create or open a database. To delete a field: 3. Click the Field tab. 1. Right-click in the form and click the Proper- ties...context menu command. The Box Properties dialog box appears. 2. Click the Field tab. The Field properties appear. 3. In the field list, select the field to be deleted. 4. Click the Delete Field button.

Figure 16.25 Creating a new field 4. Select the Table in which you want to create new structure columns.

ChemFinder & BioViz 333 User Guide 5. Click the Create Field button. You do not provide a name or other details when The Create Field dialog box appears. you create Structure columns. ChemFinder 11.0 automatically creates four columns and names them.

Administrator These columns contain no data until you enter structures into the database. Backing up databases To back up the current ChemFinder 11.0 database: 1. Click the File>Copy Database menu command. A Save As dialog box appears. By default, your Figure 16.26 Create Field dialog box copy is named YourDatabase_copy.cfx. 2. Rename your copy (if you wish), select a loca- 6. Select Structure from the Type drop-down list. tion, and click the OK button. An uneditable name is assigned to the field. A complete set of ChemFinder 11.0 database 7. Click the OK button. files is created in the selected location. Four new fields appear in the list and are named to belong to the same set of structure Moving databases columns. ChemFinder 11.0 saves only the definition of the 8. Connect the new fields to boxes by right-clicking form and information for connecting to the data- on the appropriate data box and choosing the base in the CFX file. The actual data are stored in field from the context menu field list. files with MSI and MST extensions for structure da- Adding structures to non-chemical ta, and in files with an MDB extension for non- structural data. If you want to move a database to databases another computer, you must move (for a default If you opened a database that you created using a ChemFinder 11.0 database) at least four separate program other than ChemFinder 11.0 and you want files. This number might be greater if you have sev- to add structures to it, you can create structure eral forms that access the same database. fields in any modifiable (non-attached) table. NOTE: The MSI, MST, and MDB files all have the To create a structure field: same file name, but the name of the CFX files might be different depending on how you saved them. 1. Open a database. After you move the database to its new location, 2. Right click, click the Properties... context menu open your forms to make sure the data source links command. have been retained. If ChemFinder 11.0 cannot lo- 3. In the database tree, click the table to which you cate the data source and displays an empty form, want to add structures. you will need to use the File>Database menu com- 4. Click the Field tab. mand to reconnect to the data source. 5. Click the Create Field button. If the form is connected to a remote data source on The Create Field dialog box appears. a network, you have fewer files to move. The data 6. Choose Structure from the Type drop-down list, source can remain on the remote machine, and you then click the OK button. only move the CFX file that contains your form for accessing the data. You may need to reconnect it to

334 the data source if it is not done automatically. This interest. The portal looks and behaves just like the situation is common in large organizations where target database, but without the limitations. several people access the same central data source. ChemFinder 11.0 creates a portal database when needed. For example, if you are using a database Creating a portal database CD, perform a search, and attempt to sort by for- To carry out certain operations, such as sorting mula, a message appears that offers to create a local structural data, ChemFinder 11.0 needs to create database, attach the current table, save the form, temporary tables in a database. This cannot be done and proceed with the sort. If you create the local da- in a read-only source such as a data CD. tabase, you can use the new form to get the data with full functionality and performance. Instead of accessing the read-only source directly, you can create a portal database–a local, writable database with attachments to the external tables of

ChemFinder & BioViz 335 User Guide Administrator

336 Chapter 17: Working with Data

Entering data into a database • Click the Record>Add New Record menu command. You enter data into a database by adding a new record. Adding a new record consists of three steps: • Click the Add Record icon on the • Clearing the form Record Toolbar. • Adding new data 3. All of the boxes in the form are cleared to prepare for entering new data. The Status Bar is • Committing the new entries updated to show that you are in record addition Clearing the form mode: To begin adding a new record: 1. Create a form and link it to a database. For more Figure 17.1 Status bar in record addition mode. information, see “Creating forms manually” on page 301. Adding new data The form should contain all the data boxes you To add alphanumeric data: want to view and edit. The boxes should be Click in a box with an alphanumeric field and assigned to their appropriate fields. type the data. 2. Do one of the following:

ChemFinder & BioViz 337 User Guide To add a structure: Committing the new data 1. Right-click in a box with a structure field. When you finish entering all of the data items, do 2. Do one of the following: one of the following: Administrator • Click the Commit button on the Add Record If you want to... Then... Toolbar. • Click the Commit Changes icon on the draw a structure, 1. Double-click in the struc- ChemDraw mode ture box. Record Toolbar. The ChemDraw Control • Click the Record>Commit Changes menu com- appears. mand. 2. Draw the new structure in • Perform another action such as moving to the Structure box. another record or printing. 3. Click outside to box to The new record is added to the database. complete the structure. NOTE: Selecting Commit Changes (or moving to another draw a structure, 1. Double-click in the struc- record if you have two or more records) saves the data to the ChemFinder 11.0 ture box, or Right-click and database. Do not use File>Save; clicking File>Save saves mode click the Edit in ChemDraw changes to the form layout, not changes to data in the data- context menu command. base. ChemDraw opens. Duplicating records 2. Draw the new structure in the ChemDraw window. You can create a new record by modifying an exist- 3. Click the File>Exit and ing one. Return to... menu command, To duplicate a record: or type Ctrl+W to return Click the Record>Duplicate Record menu com- to ChemFinder 11.0 and mand. insert the structure. You are in Add Mode and the form fills with import a structure, 1. Right-click in the structure data from the previously displayed record. ChemFinder 11.0 box, and click the Read When you commit the changes, you create a or ChemDraw Structure context menu new record whose fields contain the data dis- mode command. played. Before committing the duplicate, you The Open dialog box can modify fields or structure and commit appears. changes just as you would with any other new 2. Browse to a structure file, record. then click the OK button. NOTE: When duplicating records, only those fields that The file is inserted into are visible on the form are duplicated. Data in fields present ChemFinder 11.0. in the database but not visible on the form are not copied into the new record. The new record has a new Mol_ID. NOTE: See the ChemDraw User’s Guide for information about using ChemDraw.

338 Undoing data entry • Move to a different record. Before committing a new data entry, you can revert NOTE: Moving to a different record always commits the contents of the form to its previous unmodified changes first. state. Editing structures To undo your changes, do one of the following: You can edit structures by using the ChemDraw • Click the Record>Undo Changes menu com- drawing tools. You can also neaten the appearance mand. of a structure by cleaning it up. The Clean Structure • Click the Undo Changes icon on the command is used to neaten the appearance of molecules by regularizing bond lengths and angles. Record Toolbar. Since the degree of change required cannot be de- After you commit the changes, they cannot be termined a priori, the Clean Structure command be- undone. gins gently. You may need to repeat the command to get the changes you wish. For more details about Editing data how the command works, see “Structure Clean Up” in Chapter 4: Advanced Drawing Techniques of the Modifying the data in a database is performed by di- ChemDraw User’s Guide. rectly changing the data items on the form and committing those changes. Before committing a data entry, you can revert to the previous unmodified record by choosing Undo NOTE: The Formula and MolWeight fields are automat- Changes from the Record menu. ically calculated by ChemFinder 11.0 from the Structure field and cannot be edited by the user. The MOL_ID field To edit structural data: is also set automatically by ChemFinder 11.0 and cannot be 1. Do one of the following: edited. •In ChemDraw mode: Double-click the struc- To edit data: ture box. Click the data box whose data item you want to The ChemDraw Control appears. edit. • In ChemFinder 11.0 mode: Double-click the If you click on a Structure data or a picture box structure box. it is highlighted. If you click on a data box con- ChemDraw opens and the structure appears taining alphanumeric data, a cursor appears in in the From ChemFinder 11.0 window. the data box. • In either mode: Right-click in the structure To edit alphanumeric data: box and click the Edit in ChemDraw context 1. Replace it with the text or number you want. menu command. 2. Do one of the following: ChemDraw opens and the structure appears in the From ChemFinder 11.0 window. • Click the Record>Commit Changes menu command. 2. Edit the structure. 3. Click in the ChemFinder 11.0 form or close the • Click the Commit Changes icon. ChemDraw window by typing Ctrl+W when you are finished.

ChemFinder & BioViz 339 User Guide 4. Click the Record>Commit Changes menu com- If you already have a structure in a data box, that mand, click the Commit Changes icon , or structure appears in the edit window. You can modify and manipulate the structure just like any other move to a different record.

Administrator ChemDraw structure. The changes are stored. If there is no structure in the Structure data box, the To clean up a structure: edit window is blank. You can draw a structure to 1. Right-click in the box containing the structure, store in the ChemFinder 11.0 database. and click the Clean Structure context menu com- When you have finished, do one of the following: mand. • If you are editing in ChemDraw, click the 2. To save the cleaned up structure, do one of the File>Exit and Return to Structure menu command following: or type Ctrl+W. • Click the Record>Commit Changes menu com- • If you are editing with the ChemDraw Control, mand. click outside the Structure box. • Click the Commit Changes icon. The new or edited structure is now displayed, but has not yet been added to the database. Working with structures using ChemDraw Click the Record>Commit Changes menu com- Enter or edit ChemDraw structures in data boxes of mand, click the Commit Changes icon , or the Structure field type. You can work in ChemDraw directly, or work in the Structure data box using the move to a different record. ChemDraw Control. You choose the default in the The changes are stored. Structure data box Box Properties. With a few exceptions, ChemFinder 11.0 can store To set the preference: any chemically meaningful structure or reaction that can be drawn in ChemDraw. Within ChemDraw, 1. Right-click in the Structure box. you can confirm that a structure is chemically 2. Click the Properties... context menu command. meaningful by selecting it and using the Struc- 3. Use the drop-down menu in the Box Style sec- ture>Check Structure menu command. For more in- tion to choose your default: formation, see the ChemDraw User’s Guide. • ChemDraw style to use the ChemDraw Con- Two exceptions are: trol. • ChemFinder 11.0 does not support importing • ChemFinder 11.0 style to edit in ChemDraw. molecules with multiple or variable points of TIP: When ChemDraw style is the default, you still attachment such as ferrocene. have the option of editing directly in ChemDraw. Just • ChemFinder 11.0 does not recognize “bare” right-click in the Structure box and choose Edit in heteroatoms. For example, if you draw the fol- ChemDraw. lowing structure:

To edit a structure: N Double-click in the structure data box. ChemDraw opens or the ChemDraw Control ChemDraw reports an illegal valence when you appears, depending on your default. choose the Check Structure command. ChemFind- er 11.0 automatically infers hydrogen atoms to

340 main-group elements as necessary to fill their low- To view the molecular model for a structure: est acceptable valence. The structure above is regis- 1. In the Database pane of the Explorer window, tered in ChemFinder 11.0 as methylamine, double-click the Structure field to add another CH NH . 3 2 Structure field to the form. Structures and reactions drawn with query proper- 2. Right-click in the field and click the Properties... ties are generally meaningful only in the context of context menu command. a query. Query structures can be stored in a Chem- 3. In the Box Style section, select Structure (Chem3D Finder 11.0 database, but they are not treated as style) from the drop-down menu. Markush structures and are not guaranteed to be hit The Structure field displays a 3D structure. by all valid search queries. For more information, see Appendix A, “.”. ChemDraw allows you to draw many objects that have no chemical meaning. These include boxes, circles, arrows, orbitals, and others. It also allows you to assign non-chemical styles (color) to objects that have chemical meaning. ChemFinder 11.0 ignores these properties, and stores only objects with chemical meaning in structure fields. To store a ChemDraw drawing exactly as drawn, store it as a picture. You can copy and paste a Chem- Figure 17.3 Form with 3D structure field. Draw drawing into a Picture field. To rotate the model or modify the display, double- click in the field. The default tool is the rotation tool, but it also can be used to select atoms or bonds. If you right-click in the field, the context menu displayed is the Chem3D control context menu, giving you access to Chem3D commands. See the Chem3D User’s Guide for more information about using Chem3D. Figure 17.2 Form with picture field NOTE: Unlike interaction with ChemDraw, changes you NOTE: Objects stored in a Picture field have no chemical make to a model within Chem3D are not transmitted back significance and cannot be searched. to ChemFinder 11.0, and thus are not saved. You can put a picture of the Chem3D model into a database by saving the Viewing models using Chem3D Chem3D model as a bitmap or metafile and inserting it into ChemFinder 11.0 also provides access to the a Picture field. The picture does not retain a connection table Chem3D Control. This means a Structure data box and cannot be edited. can be designated as Chem3D style. Styled text Make changes to text fonts, sizes, styles, colors, and alignment with the tools on the Text menu or the Text Format toolbar. To display the Text Format toolbar, if it is not visi-

ChemFinder & BioViz 341 User Guide ble: Mol_ID. Click the View>Toolbars>Text Format menu com- To delete an entire record: mand. 1. Move to the record that you want to delete using Administrator The Text Format Tool appears. the Record commands or toolbar.

. Subscript 2. Do one of the following: Font Bold Align Bullets • Click the Record>Delete Record menu com- Left mand. • Click the Delete Record icon. The record is permanently removed. Font Size Superscript Center Right NOTE: You can delete multiple records if you use the Table view. Use the toolbar to format text in Plain Text or Memo/Rich Text data fields. Sorting data Undoing changes You can sort the database by most types of data in Before committing your text changes, you can re- a form. Sorting on the Mol_ID field, the molecular vert to the previous unmodified state. weight field, or any other numeric field arranges the To undo your changes, do one of the following: current list in increasing or decreasing numeric order according to that field. Sorting on the structure • Click the Edit >Undo menu command. field arranges the list by increasing number of at- • Click the Undo icon on the Main Toolbar. oms contained in the structure. Implicit hydrogens are not counted. Sorting on the formula field orders After you commit the changes, they cannot be the records by increasing C-H-N count (for com- undone. pounds containing carbon) followed alphabetically Redoing changes by any other elements. Formulas for compounds without carbon are sorted in alphabetical order. When you undo an action, the Redo command be- Sorting by text fields such as molecular name sorts comes active. You can reverse the effect of the the records alphabetically. Undo command by choosing the Redo command. After sorting, the database must be reset to its orig- To redo the last action performed, do one of the inal state before you can update it. following: NOTE: You cannot edit records sorted by formula or molec- • Click the Edit>Redo menu command. ular weight. However, if you attempt to sort on one of these • Click the Redo icon. fields, ChemFinder 11.0 offers to set up a database (a portal database) which allows the operation. For details, see The last action undone is reinstated. “Attaching tables from other applications” on page 330. Deleting data To sort on a field: • In the Form View, right-click in the field you You can delete the contents of individual fields by want to sort by, and click the Sort>Ascending or using the Delete or Backspace keys. You cannot de- Sort>Descending context menu command. lete a structure, formula, molecular weight or

342 • In the Data Table View, double-click on the Resetting the database table header of the field you want to sort by. To reset the database to its original state: The table is sorted in ascending order by the column you selected. Double-clicking again Click the Search>Retrieve All menu command. will sort in descending order. Changing the database scheme TIP: There is also a context menu option for sorting You can create or remove fields or tables in an ex- in Data Table view. Right-click in a column and choose isting or new database as long as the database is not Sort Column. read-only and you have permission to modify it. You may also attach, or link, tables from external Sorting in languages other than English data sources. Text that you sort must be in the same language as Use the Box Properties dialog box to perform the the default language of the system on which the da- following procedures: tabase was created, or an incorrect sort order can Do one of the following: occur. • Click the File>Database menu command. The ChemFinder 11.0 sample databases, created in English, can be sorted correctly using the following • Right-click any empty space in the form window and click the Data Source...context menu languages: command. • English The Box Properties dialog box appears, with •German the Database tab displayed. •French To add or remove a field: •Portuguese Click the Field tab. Do one of the following: • Italian • To create a new field: • Modern Spanish a. If there is more than one table, select the If you want to sort text in a different language than table that will contain the new field. the one in which the database was created, perform b. click the Create Field... button. the following procedure: The Create Field dialog box appears. 1. On a computer using the same language as the c. Replace the default name (New_Field), text you want to sort, open MS Access. select a data type, and adjust the field width 2. Open the MDB file you want to sort. (optional). Click OK when you have finished. 3. Compact the database: click the Tools>Database • To delete an existing field: Utilities>Compact Database menu command. a. Select a field. 4. After the database is compacted, close MS b. Click the Delete Field... button. Access. A warning box comes up, asking if you really The correct sort information is written into the mean to delete a field. database. When you perform a sort in Chem- Finder 11.0, the sort order will be correct.

ChemFinder & BioViz 343 User Guide c. Click Yes to delete the field. a. Select a table. b. Click the Delete Table... button. All data entered in the field, will be lost as soon as you c. Click YES in the warning box.

Administrator click the YES button. All data in all fields in the table will be lost. To add or remove a table: Click the Table tab. Do one of the following: To attach a table from another database: • To create a new table: 1. Click the Table tab. a. Click the Create Table... button. 2. Click the Attach Table... button. b. Enter a name in the Create Table dialog box. The Attach Table dialog box appears. The new table is created, with a default field 3. Select the type of database – MS Access or Ora- named ID. cle/ODBC. •To remove a table: 4. For MS Access, browse to the MDB file containing the table. Select a table, and click OK.

344 Chapter 18: Database Queries

Overview • When searching a normal text field, if the text query starts with = (for example =toluene) then You can search a ChemFinder 11.0 database by que- the search requires an exact text match. rying any field or combination of fields. You can • Text strings may contain wild cards or Boolean specify a chemical structure and/or text as the que- operators. Standard wild cards are % or *. ry. When searching text or numbers, you can use These characters are equivalent and hit any wildcards or specify a numerical range. When struc- string. Other wild cards are also possible. If ture searching, you can search by sub- or full struc- wildcards are present, they override the above ture, search for an exact match, similarity, or defaults. tautomerism, and specify how stereochemistry will be matched. You can also combine structure NOTE: Using wildcards or a = in memo fields may searching with text or numerical searching. A Find lead to unexpected results. This is because a memo field Structure command performs “duplicate”, “error”, may contain formatting information surrounding the “isotopic label”, and other special structure search- text you see, so a search like benz* may give no hits. es. Using *benz*, however, will give the same results in a The chapter describes the different types of search- memo field as in a plain text field. es and how to set up and manage searches. It con- cludes with some examples of advanced techniques. • A checkbox in the Search Preferences dialog allows you to request a full-word match. When Text searches this box is checked, a hit must contain the query as a complete word, not embedded ChemFinder 11.0, like all databases, supports text within a larger string. searching. You can search any alphanumeric field • Boolean operators are NOT, OR, and AND. for strings of text. Use text searching, for example, They may be used to combine search terms to find chemical names, or comments in a reference within one field. field. For text searches, ChemFinder 11.0 interprets the TIP: Use NOT* to search for empty fields. query, then passes it as Structured Query Language (SQL) to the relational database. Examples of queries: The following rules apply to these queries: Entry Possible Hits Will Not Hit • When searching a normal text field, a plain text string is taken as an “anchored substring,” which hits any string starting with the indicated benz Benzene, Bromobenzene substring. Benzoic acid • When searching a memo field, a plain text string is unanchored, and hits any string which benz OR Benzene, Azobenzene contains it anywhere. *bromo* Benzoic acid, Bromobenzene, Dibromobenzene

ChemFinder & BioViz 345 User Guide The following table shows query examples. =benzene Benzene Benzoic acid, Benzene-d6, Bromobenzene Entry Possible hits Administrator

C6H6 compounds with 6 carbons and Numeric searches 6 hydrogen atoms, plus any Searching numerical data allows you to find infor- number of other elements. mation such as boiling points and molecular weights. =C6H6 compounds with 6 carbons and Ranges are specified using a hyphen between the 6 hydrogen atoms and no other values at either end of the range. elements. For numerical searching, the query is a decimal value or range. If a single value is given, the number of C6N0 compounds with 6 carbons, no significant digits determines the precision of the nitrogens, plus any number of search. A hit is any value that rounds off to the que- other elements. ry. Examples of queries: C6 N1-3 compounds with 6 carbons and one to three nitrogen atoms, plus any number of other Entry Possible hits elements.

90 values from 89.5 to 90.5 Formula queries consist of element symbols and element counts or ranges. 90.1 values from 90.05 to 90.15 The following rules apply: • Symbols may be one or two letters. Symbols 90–100 values from 90 through 100, may be in upper or lower case; if there are inclusive ambiguities, the program resolves them according to rules described in Appendix C, “.”. >=90 and <=100 values from 90 through 100, • Capitalize the symbols properly and insert inclusive spaces between elements. • Use the Periodic Table to enter formulas. For >90 and <100 values from 90 through 100, more information, see “Using the periodic exclusive table” on page 428 and Appendix C, “.” • Element counts are single integers or ranges Molecular formula searches (two integers separated by a hyphen). If a count is omitted, it is assumed to be 1. Formula searching allows you to search molecular compositions. Searches can be inclusive, exact (des- • If the formula query is preceded by = (for ignated with an equals sign) or with the element example =C6H6) then the search requires an range you specify. exact formula match, containing no elements other than those indicated. If there is no =, then

346 the search is a partial match: other elements Find list may be present in the hits. Use the Find List command to retrieve records hav- • Symbols may be repeated. For example, ing specific values in any non-structure field. CH3CH3 is interpreted as C2H6. Type parameters into the Find List box as follows: NOTE: Formula searches are completely non- • If the column you search is an integer type, you structural: CH3CH2OH matches both dimethyl ether can use hyphens to indicate ranges. and ethyl alcohol because both compounds have the same condensed formula: C2H6O. • If the column you search is a number or text type, you cannot use hyphens to indicate • Parentheses may be used to group elements ranges; you must search for an exact match. and apply a count to the entire group. For example, (CH2)3 is interpreted as C3H6. NOTE: To search for a list of records using partial text (a “wildcard” search) or range of numbers, do a • Spaces or non-alphanumeric characters other search on the relevant field. than parentheses are ignored. • If the column you search is a text type, you Date searches must use quotes around any item that contains Dates might be used to track individual reaction commas. For example, you must type 1,2-Pyran runs, purchasing histories, and so on. Searching as “1,2-Pyran”. dates is very similar to searching numerical data. • You may save a list as a text file and retrieve it Ranges are specified using a hyphen between the later with the File button. values at either end of the range. Ranges may also To find a list: be indicated using inequality operators (<, >) together with the AND operator. 1. Click the Search>Find List menu command. The Find List dialog box appears. Dates are always displayed according to the preferences set in the operating system’s International control panel, but need not be input in that format. The following table shows query examples.

Entry Possible hits

Apr 11, 1971 the exact date April 11, 1971

March 31, 1971– any date in the second July 1, 1971 quarter of the year 1971

>4/ 11/71 any date after April 11, 1971 Figure 18.1 The Find List dialog box 2. Choose a field from the Column menu. 3. Paste or type a list of field parameters into the Find List text box.

ChemFinder & BioViz 347 User Guide 4. Click the OK button. Normal search by selecting options in the Search De- The list of matching records is retrieved. tails tab of the Preferences dialog box.

Administrator Structure searches You can search a ChemFinder 11.0 database by sub- or full structure. To define your search more precisely, use the query functions in ChemDraw. These are described in Chapter 9 of the ChemDraw User Manual, and in Appendix III-A: “.” in this manual. ChemFinder 11.0 matches structures in three ways: • Search type (Normal/Exact/Similarity) • Structure mode (sub- or full structure) •Tautomerism

Figure 18.3 Search details on the Preferences dialog box The query structure is highlighted in red in the hitlist structures to visualize the match. Exact searches Figure 18.2 Structure search tree The Exact search type, also known as an Identity search, is intended for use in compound registra- Search types tion, when you must know if a perfectly identical ChemFinder 11.0 supports three structure search copy of your query compound is already present in types: the database. The target must be chemically identical to the query, including stereochemistry, charges, •Normal and isotopy. It is a convenient shorthand for full •Exact structure, same-stereochemistry, and appropriate • Similarity settings of all the other options. Thus, generic atom and bond types such as R, A, and Double-or-Aro- Normal and similarity searches may be in either of matic in the query will match corresponding atom two modes: full structure or substructure. Normal and bond types in the target only if they are also of the and exact searches may also search for tautomer- same generic type. In other words, an atom labeled “R” ism. in the query must find a matching atom labeled “R” Normal searches in the target to produce a hit. If the stereochemistry of the query is unspecified, it will only hit targets A Normal search finds structures that either con- which do not specify stereochemistry. The only tain (Substructure) or match (Full Structure) the variable in an exact match search is whether or not query. When drawing a structure query, you can at- it is tautomerically flexible. tach different features to a query, such as atom lists The Search Details tab in the Preferences dialog box is and variable bond types, to perform a narrower or unavailable for Exact searches. broader search. You can also modify the results of a

348 Similarity searches ate. A Similarity search finds targets that “look like” the You can adjust the degree of similarity (from query. Similarity searches are by their nature 0 to 100%) necessary to produce a hit by using the “fuzzy”. What “looks like” means is obviously sub- slider on the Search Type tab of the Preferences dia- ject to interpretation and depends on the applica- log box. tion. In medicinal applications the drug absorption properties are relevant. In a toxicological context Structure modes the metabolism is of interest. For database queries, The term “Structure Mode” refers to whether the the similarity in functional groups is what is mea- query defines a substructure of the compounds in sured. A quantitative measure of similarity, know as the database being searched, or the full structure. In the Tanimoto algorithm after its discoverer, is cal- this context, it is important to note that “full struc- culated. For more information, see Appendix III- ture” does not mean the same as “exact”. When you D: “.”. specify the “Exact” search type, the structure mode Similarity searches may be either full- or substruc- is always full structure, but you may choose the full ture. In a substructure similarity search there is no structure mode with any of the three search types. penalty if the target contains extra, non-similar as- See “Full structure searches” on page 350 and “Ex- pects. In a Full Structure similarity search, the re- act searches” on page 348 for more details. sults are guaranteed to include all hits you would obtain from a substructure search with the same Substructure searches query. Usually, they include additional hits. For this A substructure search finds structures that contain reason, similarity searches are useful if you have a the query, plus any additional attachments at the general idea of the types of compounds you are open positions. This is the default search mode. looking for, but don’t have a precise conception of The substructure is highlighted in red in the hit-list the target compound. structures. Using the ChemDraw ActiveX toolbar, Unlike exact searches, similarity searches do not you can attach different features to a query, such as highlight matched portions of the target com- atom lists and variable bond types, to perform a pounds. Similarity searching matches general struc- narrower or broader search. For more information tural features and not specific atoms and bonds, so about what query features you may use and how highlighting specific areas would not be appropri- these features affect a search, see “Changing the

ChemFinder & BioViz 349 User Guide scope of a search” on page 456. may allow fragments to overlap in the target struc- : ture. For example, if you perform the following sub-

Administrator This substructure will hit structure query with Query fragments may overlap in query target selected:

Figure 18.5 Fragment query The hit list will include the following:

Figure 18.6 Example of substance hit in a fragment query The dot indicates an atom shared between the two fragments. The hit list will not include this molecule if the overlap option is deselected. Tautomeric searches A tautomeric search is one in which the location of single and double bonds may vary from query to and other molecules target. A hit occurs if, in addition to the atom types Figure 18.4 A simple substructure search matching, the target possesses a tautomeric form whose bond orders match the query’s. Which tau- NOTE: In searching substructures, ChemFinder 11.0 tomers are recognized is under some degree of con- finds the substructure query regardless of its orientation or trol. Tautomers of the form: drawing presentation in the targeted molecules. Bonds shown in bold above are actually highlighted in red in ChemFinder 11.0. Figure 18.7 Tautomeric structure Full structure searches are always recognized when at least one of X and Z A full structure search finds structures that com- is not carbon. The lone pair may include a migrating pletely match the query. If you do not specify stere- proton. It is also possible to include tautomers in ochemistry, or use generic atom or bond labels, you which X and Z may both be carbon. The choice may get more than one hit. You may also get more must be made at the time the database is created or than one hit if there are duplicates in the database. upgraded, because it affects how structures are For more information, see “Stereochemistry” on stored. page 351 and “Exact searches” on page 348. Mesomers (resonance structures) are also picked up Fragment searches in tautomeric searches. Tautomerism involving formation or cleavage of sigma bonds is not currently You can draw more than one structure or structure supported. The principal categories are ring-chain fragment in your substructure search query. In the tautomerism, as in the open vs. cyclic forms of sug- Search Details tab of the Preferences dialog box, you ars, and valence tautomerism.

350 Tautomeric searching is slower than non-tautomer- fied as ranges) to a query structure. For example, ic, but is the mode of choice when you think the tar- you might specify that two atoms must be between get might have a slightly different layout of double 4Å and 5Å apart, or that two planes must be sepa- bonds. rated by 80-100°. ChemFinder 11.0 can then use these properties to refine a search. See the Chem- Stereochemistry Draw User’s Manual for information on how to add You can specify whether or not you want a struc- 3D properties to structures. ture search to consider stereochemistry. Given a Searching with R-groups structure with one or more stereocenters, you can store four different possibilities: ChemFinder 11.0 supports queries using R-tables, including multiple R-tables. Queries containing • A given absolute configuration. To specify this, large numbers of R-groups or large numbers of R- centers must be drawn with stereo bonds, and values are not advisable however, because Chem- the entire structure marked Abs (CHIRAL). Finder 11.0 pre-processing expands the query, sub- • A racemic mixture of the drawn configuration stituting all combinations from the R-group and its mirror image. This is drawn as above, table(s). but without the Abs (CHIRAL) mark. • An unmarked structure, representing unknown Alternative groups stereochemistry, or a mixture of all possible ste- Instead of submitting multiple queries on structures reo-isomers. that share a common substructure, you can submit • A given relationship between centers. That is, a a single query with the parent structure and variable known orientation of the substituents with functional groups or substructures. The parent respect to each other, rather than a known structure is drawn with attachment point(s) that re- absolute configuration. To specify this, centers fer to a list of alternative groups that you define. are drawn, not with the standard hashed and wedged bonds, but with thick stereo bonds. If these options are checked in the Search tab of the Preferences dialog, then any stereochemistry indicated on the query must be matched by the target. For more information on changing searching preferences, see “Setting search details preferences” on page 357.

3D properties 3D queries are particularly useful in pharmacoph- ore searching where you are looking for a particular 3D relationship among atoms and bonds, for example in a series of potential receptor ligands. You can create a 3D query in ChemDraw Pro by adding ge- Figure 18.8 Alternative groups ometries (lines, planes, etc.) and constraints (speci-

ChemFinder & BioViz 351 User Guide Defining an alternative group Keys, or Nicknames to create atom labels for To define an alternative group: each variable. 1. Click the query icon to begin the search. R Administrator 2. Right-click in the structure window and click the 1 Cl Edit in ChemDraw context menu command R

TIP: You want to open ChemDraw because you will CH2OH need more space than the structure window provides. Ph ChemDraw opens to a new page. 3. Draw the parent compound. Figure 18.10 Adding the alternative groups 4. Label the atom where the alternate groups will 9. Add the Attachment Points: attach with a generic label such as R. a.Click the diamond shaped Attach- ment Point tool on the Chemical Sym- 5. Click the Alternative Group query tool . bols palette. 6. Drag with the tool in an open part of the page to b. Click the open atom position on each sub- create an area large enough to draw the alterna- structure fragment. tive groups. 7. Type a title in the Alternative Group Title box. TIP: Alternatively, the HotKey “.”(period) can be The title must match the atom label in the parent used to add attachment points. structure (G, in Figure 18.8, but we’ll use R in

this example). R

Title box 1 1 Cl R

1 CH2OH

1 Ph

Figure 18.11 Completed alternative group query NOTE: In the above procedure, the parent structure was Figure 18.9 Adding a title to an alternative group drawn, then the R-Group table was added. In fact, the order 8. Draw the substructure fragments in the Alterna- doesn’t matter. You may create the R-Group table first, then tive Group box. Use the single bond tool to draw the parent structure. In either case, as soon as a generic define a fragment, and the text tool, atom Hot- atom label in the structure matches the group title in the R- Group table, a hollow attachment point symbol appears next to the label in the parent structure. 10.Type Ctrl+W to return to ChemFinder 11.0. The structure and the R-Group table appear in the structure window. 11.Continue the query as usual.

352 Reaction searches For example: You can search and store reactions. In a reaction, F Cl one or several compounds (reactants) are trans- does not hit formed into other compounds (products). Individ- ual reactants (or products) are separated from each O OH other with plus signs. The reactants are separated from the products with an arrow. Reactions may have multiple steps, for example F Cl F Cl (A) (B) (C) (D). Here, (A) is the reac- Figure 18.13 Query does not hit because it does not tant and (D) is the product. (B) and (C) are interme- contain the reaction center. diates for the complete reaction. when the Reaction query must hit reaction center pref- A multi-step reaction is actually a shorthand nota- erence is selected. Even though there is a C-F bond tion for many related reactions. In the example in the target reactant and a C-Cl bond in the target above, (B) is an intermediate for the complete reac- product, these bonds do not participate in the reaction, but it is also a reactant relative to (C) or (D). It tion, which really affects another part of the com- is also a product relative to (A). The complete reac- pound. If you deselect the Reaction query must hit tion implies many subreactions, such as: reaction center preference, this query hits the target (B) (D) and (A) (B). above. Reaction centers When creating reaction queries, it is important to consider what sort of information you are really The most important part of a reaction is the part looking for. Suppose you want to convert n-decanal that actually changes from the reactants to the to n-decanol: products. This part, which probably includes a number of atoms and bonds, is called the reaction O center. For example, only the bold bond in the figure below (and the two atoms on either side) is part of the reaction center. The rest of the structure is OH unchanged from the reactant to the product: Figure 18.14 Reduction of n-decanal O OH Are you really interested only in these two compounds? You might be interested in any reaction that converts a straight-chain aldehyde to the alcohol: F Cl F Cl H H Figure 18.12 Reaction center example H H O OH By default, ChemFinder 11.0 considers reaction centers whenever you search for reactions. Chem- Finder 11.0 assumes that any atoms and bonds that H H change in the query must be part of the reaction Figure 18.15 Generic aldehyde reduction query center of the target. Since the corresponding n-octanal n-octanol

ChemFinder & BioViz 353 User Guide reaction would probably occur under very similar would be mapped like this:

conditions, it is a reasonable thing to look at. Gen- 3 3 O O erally, you want to use substructure queries that in- 6 Rxn OH 5 H2O 6 Administrator clude little beyond the reaction center in question 2 5 2 1 OH 4 1 O Rxn when you are searching for reactions. 4 NOTE: ChemFinder 11.0 supports several query proper- Figure 18.18 Alternate possible atom map for esterifica- ties to allow you to specify exactly how a bond participates in tion a reaction center. For more information about these proper- ChemFinder 11.0 uses atom-to-atom map informa- ties, see “Setting search details preferences” on page 357. tion to determine reacting centers for reactions. If Atom-to-atom mapping only some atoms are mapped, ChemFinder 11.0 uses that information and does not worry about the The second most important part of reaction search- specific fates of the other atoms. For example, if ing is the atom-to-atom map. You can specify maps you don’t know (or don’t care) about the mapping in ChemDraw, where they are stored as part of the of some atoms, you can leave them unspecified in data about a reaction. Maps are used during search- the atom-to-atom map. ing to resolve certain types of structure search hits. By default, atom-to-atom mapping is not displayed Consider a simple esterification reaction: within ChemFinder 11.0. To turn on this display, se-

O O lect Atom-to-Atom Map on the Structure sub-menu OH of the View menu. For more information, see “Set- H2O OH O ting preferences” on page 423. Figure 18.16 Esterification example NOTE: For information about specifying atom-to-atom Does the ester oxygen come from the acid or the al- maps with ChemDraw, see the ChemDraw User’s Guide. cohol? You specify the fate of individual atoms Searching for reactants through an atom-to-atom map. In reality, the ester oxygen in this reaction originates in the alcohol, so If you know what starting materials you are interest- the atom-to-atom map looks like this: ed in but don’t know their products, you might perform a reactants query. A reactants query is very 3 3 O O similar to a reaction search, except that there is OH 6 5 H O 4 Rxn 2 nothing to the right of the arrow. For example, con- 2 5 2 1 OH 4 1 Rxn O 6 sider the query:

Figure 18.17 Atom map of esterification O By matching numbers across the arrow, you can see where atoms move during the course of the reac- O tion. The other reaction (not observed experimen-

tally), where the ester oxygen comes from the acid, O Figure 18.19 Sample reactants query If you are doing a substructure search, this finds any reactions in which maleic anhydride or a compound containing a maleic anhydride substructure is consumed or transformed.

354 Searching for products To perform a combined search: If you know the desired end product but not how 1. Do one of the following to clear the form: to get there, you can do a products query. A prod- • Click the Search>Enter Query menu com- ucts query is similar to a reaction search, except that mand. there is nothing to the left of the arrow. For example, consider the query: • Click the Enter Query icon on the Search toolbar. 2. Enter the structural query, if any. 3. Enter the text and/or numeric queries in the appropriate boxes. Figure 18.20 Sample products query 4. Do one of the following: If you are doing a substructure search, this finds any • Click the Search>Find menu command. reactions in which bicyclo[2.2.1]heptane or a compound containing this substructure is produced. • Click the Find icon on the Search Tool- bar. Searching for intermediates Combined searching example: Rarely, you may be looking for reactions for which you only know something about an intermediate. Suppose you want to find all molecules in the An Intermediate Search is very similar to a normal CS_Demo database that contain a benzene ring and reaction search, except that there are arrows on which have names related to penicillin. both sides of the target structure. For example, con- 1. Click the Search>Enter Query menu command. sider the query: 2. Draw a benzene ring. RCC O 3. Enter *penicillin* in the Molname field. Figure 18.21 Sample intermediates query 4. Check that the Search>Substructure option is This finds any reactions containing the Ketene selected. structure shown as an intermediate. 5. Click the Search>Find menu command. NOTE: ChemFinder 11.0 cannot predict products or You get 2 hits of molecules whose names contain intermediates of reactions. It finds this information only if it penicillin and whose structures have an aromatic is already present in the database. ring of six carbon atoms. Combined searches NOTE: In a combined search, progress reports are given only during the structure search part. When the counters at You can combine structure searching with text the bottom of the screen are advancing, structures are being searching to find a specific class of compounds. For searched. You can press Esc to end a search during the struc- example, you may want to find all compounds in the ture searching. You cannot end a search during the SQL database whose names end in mycin and whose searching by pressing Esc. structures contain a phenyl ring. Because you are entering multiple queries in different data boxes, SQL searches there is an implicit AND condition between data SQL (Structured Query Language) can be used to items in different fields. create powerful searches. The details of the lan-

ChemFinder & BioViz 355 User Guide guage are not discussed here. To set Search Type preferences: Queries beginning with a backslash (\) are taken as 1. Right-click in the Structure box and click the straight SQL, and passed directly to the database as Preferences... context menu command.

Administrator the WHERE clause of the SQL query. These must The Preferences dialog box appears, with the contain column names and punctuation as dictated Search Type tab displayed. by SQL. For example, a valid query might be \[molname] like 'benz*' and [bpoint] > 200. A straight SQL query may be entered in any box of the form which contains non-structural data. The SQL query is not associated with the box in which it is entered. Query procedures Searching includes the following steps: • Setting the search type preferences (Structure searches only). • Entering the query in the form. • Submitting the query to the search engine. Figure 18.23 Search type preferences To perform a search, use the Search menu or the corresponding tools in the Search toolbar. 2. Take the appropriate action:

Enter Retrieve Previous Restore Restore If you want to Then click Query All Query List Previous List find structures containing a Substructure. common structural component

Find Find Current Save Find find a particular structure Full Structure. Molecule List List

Figure 18.22 The Search toolbar search with variability in Normal The following procedures describe searching with the query the Search menu. You may use the Search toolbar instead for most procedures. search for a precise match Exact Setting search type preferences You can set preferences for the type of structure for which you want to search.

356 The Search Details tab appears. If you want to Then click

find structures having Similar and set features similar to the query the degree of similarity.

NOTE: The higher the value, the fewer hits found.

find structures that are Tautomeric. tautomeric forms of the query Figure 18.24 Search details preferences 3. Take the appropriate action: match bonds as drawn, Non-tautomeric without tautomeric forms If you want to Then click

3. Click the OK button. Allow uncharged non- Hit any charge on TIP: You don’t always have to access the Preferences dialog carbon atoms in the heteroatom. to change search preferences. Switches on the Search menu query to match charged allow you to toggle Substructure/Full Structure and Nor- atoms in the target. mal/Similarity. NOTE: Charged atoms in Setting search details preferences the query must always match You can set preferences for the details of each charged atoms in the target, search. regardless of this setting. To set Search Details preferences: Allow uncharged Hit any charge on 1. Click the File>Preferences menu command. carbon atoms in the carbon. The Preferences dialog box appears. query to match charged 2. Click the Search Details tab. carbon atoms in the target.

NOTE: Charged atoms in the query must always match charged atoms in the target, regardless of this setting.

ChemFinder & BioViz 357 User Guide settings for special query conditions. On this tab, If you want to Then click there are checkboxes for: • ignoring implicit hydrogens

Administrator Allow hits to contain Permit extraneous frag- • loose delocalization (see “Normalization” on molecular fragments in ments in full structure page 455 for details) addition to the structure searches. hit by the query. • full word text matching • case-insensitive matching (for Oracle) Allow fragments in the Query fragments can • matching stereochemistry query to overlap (share overlap in target. The only box that is checked by default is the Match one or more atoms) in Stereochemistry box. the target. Setting stereochemical search preferences Require that any reac- Reaction query must hit The Stereochemical Search Preferences dialog box tion center present in reaction center. is activated from the Tuning tab of the Preferences di- the query overlap with alog box. reaction centers in the To set Stereochemical preferences: target. This preference applies only to reaction 1. Click the File>Preferences menu command. searching. The Preferences dialog box appears. 2. Click the How button on the Tuning tab of the Prohibit generic struc- Generics hit only Preferences dialog box. tures from hitting any generics. The Stereochemical Search Preferences dialog other structures in a box appears. query.

Require full-word text Text: match full word matching. If you do not only check this box, the query will hit any matching text fragment.

Require that the stere- Match stereochemistry ochemistry of the target and click How to set structure match that of how the stereochem- the query structure. istry is matched.

Tuning Figure 18.25 Stereochemistry search preferences The Tuning tab of the Preferences dialog box has

358 3. Set the Tetrahedral stereo center hits: 5. Click the OK button. Entering query mode If you want a tetrahedral Then... stereocenter in the query To clear the form and enter Query Mode: to... Click the Search>Enter Query menu command. You are in Query mode. match the target exactly. in Tetrahedral stereo In Query mode: center hits, click Same. • The form background color changes. match same or opposite in Tetrahedral stereo • QRY appears in the status bar. configuration at the center hits, click Either. • Form boxes which do not permit data entry center of the target. become editable for entry of queries. • Form boxes are displayed according to their match any target. in Tetrahedral stereo visibility properties. For more information, see center hits, click Any. “Hiding data boxes” on page 311.

match a relative relation- click Thick bonds repre- Entering and submitting a query ship between centers sent relative stere- To enter the query: ochemistry. 1. Position the cursor over the field you want to search and click to select it. NOTE: When Thick bonds represent relative 2. Enter the query in the data boxes. stereochemistry box is cleared (default), thick bonds 3. Click the Search button on the Query Mode box. are interchangeable with hash/wedge bonds. When the box is checked, and Tetrahedral stereo center hits is set to Same, a query marked with thick bonds will only hit a target that has the same relative relationship between centers.

4. Set the Double bond hits: Figure 18.26 The Query Mode box. ChemFinder 11.0 searches. The number of hits If you want the Then in is shown in the Status Bar at the lower right configuration of a corner of the window. double bond in the query to NOTE: If a search gets no hits or an error occurs, an alert appears and you are returned to Query mode to enter a different query or modify the current one. match the target struc- Double bond hits, click ture exactly. Same. The hit list is a subset of the complete database. You can browse it as you would any database using the Record commands in the Record menu or tool- match any configura- Double bond hits, click bar. tion in the target. Any. For example, to view the hits in tabular form:

ChemFinder & BioViz 359 User Guide Click the View>Data Table menu command. Entering a structural query Stopping a search To begin a structural query:

Administrator To stop a structure search in progress, press the Esc 1. Do one of the following to clear the form: key. The query stops and you return to browse • Click the Search>Enter Query menu com- mode. mand. NOTE: Only queries that involve structural data (struc- • Click the Enter Query icon on the ture, molecular formula, and molecular weight searches) can be stopped in this manner. SQL searches and searches that Search toolbar. involved non-structural data cannot be aborted. 2. Do one of the following to place a structure into a data box: Refining a search • Double-click in the structure box and edit You can refine a hit list of one or more records by with the ChemDraw Control. entering a query that searches only the hit list, not • Right-click and click the Edit in ChemDraw the entire database. context menu command. To refine a search: • Right-click and click the Read Structure... context menu command to open an existing 1. Verify that the Search>Over Current List menu molecule file. option is selected. •Use the Edit>Paste menu command to insert 2. Do one of the following: a structure from the clipboard. • Click the Search>Enter Query menu com- 3. Click the Search>Preferences menu command. mand. 4. Click the Search Type tab. • Click the Enter Query icon on the 5. Select the appropriate options. Optionally, select Search toolbar. options on the Search Details tab as well. ChemFinder 11.0 searches over the previously 6. Do one of the following: retrieved hit list. If no hits are found, a mes- • Click the Search>Find menu command. sage appears asking whether to search over the entire database. • Click the Find icon on the Search Tool- As long as the Over Current List switch is on, each bar. search further refines the current list. Use the Re- The status bar counters indicate search progress. trieve All command to reset. You may also use the When the search is complete, the form displays the Restore Previous List command, which acts like a first hit. The list you can browse is limited to the “Back” button. Restore Previous List goes back one hits. For Normal or Exact searches, the hit portion in the history, including any “Retrieve All”s you of each molecule is highlighted in red. If a search might have done. doesn’t find any hits, you are returned to query mode. TIP: You can change the highlight color in the preferences dialog. For example, to show no highlighting, choose black as the highlight color. See “Color preferences” on page 424 for more information.

360 Using the current molecule as a query • Click the Search>Find Current Mol menu com- As you browse through a database, you may submit mand. any structure on the screen as the structural query. • Click the Find Current Molecule icon Often, you use similarity or substructure searches on the Search Toolbar. (see above) with this type of query to find related compounds. ChemFinder 11.0 begins the search and displays the search status on the lower right corner of the status To use the current molecule for a query: bar. When the search is complete, the form displays 1. Using the Record commands, go to the record the first hit, and the list you can browse is restricted containing the structure that you want to use as a to the records hit by the query. query. Entering a reaction query 2. Click the Search>Current Mol As Query menu command. The general procedure for creating a reaction query All boxes of the form are cleared except the is very similar to creating a structural query. structure so that the molecule on display can 1. Do one of the following to clear the form: be used as part of the query. You can then continue with the query as if you had drawn the • Click the Search>Enter Query menu com- structure from scratch. mand. Finding the current molecule • Click the Enter Query icon on the Search toolbar. The Find Current Molecule command, located in the Search menu and on the Search toolbar, is sim- The form clears. ilar to the Current Mol as Query command dis- 2. Enter the query: cussed above. As you browse through the database • Double-click in the Structure box. you may find a molecule that interests you, and •The ChemDraw Control appears. want to find other related records. • Draw the structure or substructure or reac- The Find Current Molecule feature lets you per- tion in the From ChemFinder 11.0 window. form a quick structural search of the structure currently being displayed on the form. However, this • Click somewhere in the form outside the feature does not allow you to enter other search Structure box. terms. The type of structure search (complete 3. Optional: enter more query terms in the other structure, substructure, and/or similarity) is deter- data boxes for a combined search. mined by what you have selected in the Search 4. Select or deselect the Search>Substructure menu menu. option, as appropriate for your query. To find the current molecule: NOTE: The Similarity option is not available for 1. Browse to the record containing the structure of reaction queries. interest. 5. Do one of the following to search: 2. From the Search menu, choose the type of structure search you want to perform. • Click the Search>Find menu command or... 3. Do one of the following: • Click the Find icon on the Search Tool- bar.

ChemFinder & BioViz 361 User Guide The search proceeds as with simple structure • Missing Stereochemistry—Finds structures searching. with atoms capable of tetrahedral or double bond stereochemistry, but drawn as “unspeci-

Administrator Special structure searches fied”. • Charged/Radical—Finds structures with rad- The Find Structures submenu on the Search menu icals or charges. provides for several common types of searches that • With Isotopic Labels—Retrieves records con- would be awkward or arcane to conduct using reg- taining a structure with an atom that either has ular means. As with other searches, all of these a mass number, or has an Isotopic Abundance searches operate within the current record set if the attribute. Over Current List option is in effect. Otherwise, the whole list is searched, regardless of how many • Query Structures—Locates structures with records are currently displayed. any generic variability such as atom types (R, A, M, Q, X, Alkyl, Aliphatic, EDG, EWG), bond types (single-or-double, etc.), variable charge, element lists ([C,N,O]), ring bond count, etc.

• 3D—Locates structures that could be targets in a 3D search. These are structures scaled in Angstroms and having Z coordinates. Both conditions must be met. Structures that meet only one of these conditions can be found by using the With Errors search. • Rings—Finds any of the following types of ring structures (selectable from a submenu): •Bridged •Spiro •Fusion Figure 18.27 Find Structure menu • Highly condensed—Rings sharing at least These are generic searches, made without entering four bonds with others in the group, where any query information. The options are: the group has at least seven rings. • Necklace—A ring bridging at least one other • Empty Structures—Locates records contain- ring half its size or less. ing no structure. It is equivalent to specifying a molecular weight of zero in a regular search. It • Polyhedra—A group of rings each of which is provided because the latter method is a bit is fused to at least two others in the group. obscure. • Duplicates—Locates all records whose struc- • Reactions—Locates structures that are reac- tures duplicate at least one other. tions. The same effect can be achieved by If Clustered is selected, the query will be a list of entering a bare arrow as a structure query. duplicates only, clustered together (that is, a • With Stereo Centers—Finds structures con- sorted list). This makes duplicates easier to taining tetrahedral stereochemistry.

362 compare, but you cannot edit records displayed • Valence/charge—Flags structures containing in a sorted list. an atom with an impossible valence or charge. If Unique Structures Only is selected, the query Sometimes correctable. will be the same as the parent list, but with only • Net charge present—Flags structures con- one unique copy of each duplicate structure. taining a net charge. This option is not checked NOTE: The Duplicate search must be performed in Full by default because it is not normally useful. Structure mode. If the Search type is set to Substructure, you Not correctable. will get an error message reminding you to reset the search • Unrecognized atoms—Flags structures con- type preference to Full Structure. taining an atom that was not interpreted by • With Errors—Locates records with possibly ChemFinder 11.0. Such atoms typically have faulty structures. Depending on the “error”, atom type R with a greyed text label containing and whether the database is read-only, it may be question marks. Not correctable. possible to automatically re-register the struc- • Mass imbalance—Flags reactions in which ture with a corrected version. By default, this the molecular formulae of reactants is different scan begins at the currently displayed record from products. Not correctable. and proceeds to the end of the record set, or • Doubly drawn atoms—Flags structures in until the scan is aborted. You can change this which two atoms are very close together and at by unchecking the box at the bottom of the dia- least one of which lacks a label. (Also, to qualify log box. as a doubly drawn pair, the combined valence of explicit bonds must not exceed the capacity of either atom.) You get this sort of structure when attempting to draw a bond from an existing atom, but miss and accidentally create a new atom. ChemDraw flags these cases with a wavy red box.

• 3D not scaled in Angstroms— Flags structures with Z coordinates not scaled in Angstroms. Such structures will not be struck in a 3D search. • Miscellaneous—Presently, this checks one thing: that isotopic masses seem reasonable. • False stereomarks—flags stereochemical indicators such as a wedged bond on an atom that Figure 18.28 Find Structure with Errors dialog box is incapable of stereochemistry because of its The following categories of structural “error” are geometry. In a normal search, such indicators treated: are ignored. The option allows you to find all such stereochemical indications and correct any • Ambiguous stereochemistry—Flags struc- errors. tures with ambiguously drawn tetrahedral or double bond stereochemistry. Not correctable.

ChemFinder & BioViz 363 User Guide To perform a With Errors search: if you want to... then click... 1. Select the categories of interest. 2. Click the Scan button. Administrator stop the scan. Stop Scanning When a structure is flagged, its record is dis- This leaves you on the last played, the offending atom or bond (if any) is record that exhibited a “flashed” and an alert offers the user several problem choices.

The options are: “flash” the problematic Flash atom or bond. if you want to... then click... This button only appears when the error revolves ignore the error and Continue around an atom or bond. continue checking the Clicking the button creates same structure. a circle that moves toward the atom/bond, drawing rewrite the MST record, Reregister the eye to it. thus correcting the problem. Managing queries The Register (and like buttons) will not appear if ChemFinder 11.0 9 introduced a new tool to man- the database is read-only or age queries. The Queries Tree Control in the Ex- if re-registering would not plorer window maintains a list of search queries correct the problem. from the current and previous sessions. Queries are associated with forms, and the query list is saved when you save the form. When you open or activate re-register other records Rereg. Sim. Recs. an existing form, the tree updates to show only the that exhibit the same type (Re-register Similar queries for that form. of error automatically. Records) Each time you carry out a search or list operation, a new query is generated in the tree. A name is as- suppress all alerts and re- Reregister All signed to the query, and it is displayed in the tree register all records that may along with the size of the list (number of hits) and a benefit from it. brief description. The generated name is “Q*”, where n is a sequential number, and * indicates that leave the current record as Skip to Next Record the query has not been named or marked for saving. is (uncorrected) and continue the scan from the CAUTION: Depending on your preference settings, next record. unnamed queries may be automatically discarded. See “Saving and restoring lists” on page 366 for details.

364 To activate the Queries tree control: if you want to... then choose... 1. Click the View>Explorer Window menu option. 2. Click the Queries tab on the Explorer window to display the Queries tree. merge the hits of the selected Restore List query with the current list. See Queries are listed as “children” of the database (dis- “Restoring a hit list” on page played as Full List). When you select Search Over Cur- 367 for details. rent List from the Search menu before performing a query, it is displayed as a “child” of the previous list. apply the query’s color to a plot Color On Plot (The current list is indicated with a frame around of the intersection of the the colored box.) selected query with the current list. (This is the same as single- Database (Full List) click on the query.) Current list (marked with a frame) choose a different query icon Change Color “Search Over Current List” query (child list) color from the color picker dialog.

modify the query and/or rerun Restore Query it.

Figure 18.29 The Queries tree Restore Query goes to Query mode and displays the structure. To restore a query: You may modify the query, then Double-click a query. rerun it manually. TIP: Double-clicking the root item, Full List, has the same effect as choosing Retrieve All from the Search save the query to a separate file, Save Query... menu. with extension .cfq.

The Queries context menu mark the query so it will be Keep saved (as named) when the form When you right-click on a query, you display a menu is saved. with commands to manage the query. This has no effect unless the if you want to... then choose... Query Saving preference has been set to Discard unnamed queries. See “Saving and repeat the search using the Rerun restoring lists” on page 366. selected query. (This is the same as double-clicking on the query.)

ChemFinder & BioViz 365 User Guide Domains if you want to... then choose... If you are browsing a list other than the full database, you can make it seem that the database con-

Administrator delete the selected query from Remove sists only of the current “child” list. the tree. Click the Search>Domains>Set Domain to Current The next time you save the List menu command. form, this query will be lost. If The current list acts like a full database. For you delete by mistake, you can example, a Retrieve All command will retrieve close and reopen the form only this list; without selecting Search Over Cur- without saving. rent List, searches will go over it only, etc. To reset searches to the full database: rename the query. Rename Click the Search>Domains>Reset to Full Database When the Query Saving prefer- menu command. ence has been set to Discard NOTE: Set Domain to Current List remains in effect unnamed queries, this has the until cancelled. If you save the form, it will be saved with same effect as Keep. the form file and will still be in effect when you open the form again. for all queries at the same depth Sort Folder in the tree, sort alphabetically by Saving and restoring lists name. You can save queries individually as .cfq files (as You also use the context menu to display the Query with previous versions of ChemFinder 11.0) or au- Properties dialog box. In this dialog box, you can tomatically when saving the form. The old com- modify the query name, add a comment, or change mands for saving and restoring lists (as .cfq files) the color used in plots. Text entered in the Com- still appear on the Search menu, and on the context ments box will replace the standard description dis- menu displayed when you right-click on a specific played along with the number of hits. query. If you close a form without having saved your queries (or other changes), you are prompted to save or discard changes. On the General tab of the Preferences dialog box, there is an option to save all queries (the default), or only those that have been renamed. If you select this option, there are two ways to save a query with the form: • Rename the query, either with the Rename command in the context (right-click) menu, or from the query properties dialog box (also accessed Figure 18.30 The Query Properties dialog box from the context menu.)

366 • Mark the query with the Keep command on the 2. Type a filename for the hit list, and click the Save context menu. Query saved in this way retain button. their standard name. The file consists of a list of values of the primary key of each record in the hit list. If there is no primary key, the molecule ID is used. To edit a saved hit list, open the text file with a text editor such as Notepad and edit the values you want changed. Restoring a hit list Once you have saved a hit list, you can perform another search and then integrate the results from the second search with the results from the first. Thus, you can perform Boolean operations on different searches. To integrate the results of two searches: Figure 18.31 General preferences 1. Perform a search and save the hit list. Saving a hit list 2. Perform another search. Create a query and perform the search. See “Enter- 3. Click the Search>Restore List menu command. ing and submitting a query” on page 359 and “En- The Open dialog appears. tering a structural query” on page 360 for more 4. Browse to the previously saved list you want to information. integrate with the current hit list, and click the Open button. 1. When you have received the hit list, click the Search>Save List menu command. The Restore/Merge List dialog box appears. The Save As dialog appears for you to save the hit list as a text file.

Figure 18.33 The Restore/Merge List dialog box 5. Select the integration option and click the OK button. • Replace—discards the current hit list and displays the records from the hit list you chose to open. Figure 18.32 The Save As dialog box

ChemFinder & BioViz 367 User Guide • Intersect—displays only those records that the CS_Demo database that contain a benzene sub- appear in both the current hit list and in the structure and have molecular weights between 50 saved hit list. This is a Boolean AND opera- and 200. After you perform this combined search,

Administrator tion. you want to find which of these compounds do not • Subtract—displays only those records that contain a carbon-nitrogen bond. By integrating hit- are in the current hit list but are not in the lists, you can perform this search. saved hit list. For example, if the current list To create the hitlist for the first part of this search: contains records, 1, 2, 3, 4, and 5, and the 1. Open the CS_Demo database. restored list contains records 4, 5, 6, and 7, then only records 1, 2, and 3 will be dis- 2. Create the first query by drawing benzene in the played. This is a Boolean NOT operation; it Structure data box and entering 50-200 in the shows the records in the current list that are Molecular Weight Data Box. not also in the restored list. 3. Search the query. • Union—displays all records in either the You get 75 hits. current list or the saved hit list. This is a 4. Click the Search>Save List menu command. Boolean OR operation. 5. Save the hitlist as benz.txt. • Subtract from—displays only those records To create another hitlist for the second part of the that are in the saved hit list but are not in the search: current hit list. This is the same as Subtract, but with the order of the lists reversed. 1. Draw the query shown below in the Structure Data Box. The hit lists are integrated. You can browse and save this new hit list just as any other hit N list. C

NOTE: If you merge two lists and get an empty result, 2. Search the query. an alert appears and the list reverts to the previous list. You get 103 hits. 3. Click the Search>Save List menu command. Search examples 4. Save the hit list as c-n.txt. The following are examples of searching options. Integrate the two hitlists: By specifying atom and bond properties, you see 1. Click the Search>Restore List menu command. how to use the query functions in ChemDraw to 2. In the Open dialog box, open the benz.txt file. search the database more effectively. All substruc- 3. In the Restore List dialog box, click the Replace ture search query properties recognized by Chem- radio button, then click the OK button. Finder 11.0 are listed and described in Appendix A, “.”. You return to your first list of 75 hits 4. Click the Search>Restore List menu command. Working with multiple hit lists 5. In the Open dialog box, open the c-n.txt file. A detailed example of how you can use hitlist man- 6. In the Restore List dialog, click the Subtract radio agement to perform specific, sophisticated searches button, then click the OK button. follows. The hit list is reduced to the 60 records with Suppose you want to search for all compounds in compounds containing a benzene substruc-

368 ture, not containing a C-N substructure, and ChemDraw Pro, may look like this: having molecular weights between 50 and 200. This atom may be any non-hydrogen atom If you had chosen the Replace option in the last step, then only the C-N records would be displayed. A Choosing Intersect would display those records in ei- S/D This bond may be single or double ther list. Finally, choosing Union would display all [S,Se,Te] records from both lists. This atom must be S, Se, or Te

Using atom lists Figure 18.35 Specifying bond and atom types in a query Using the text tool in ChemDraw, you can enter in a The “A” label denotes that the atom may match any structural query a list of possible atom types, one of atom except hydrogen. The indicator near the bond which must match in the target compound. indicates that the bond has been defined; in this If you want to search for molecules containing a case, in the Bond Properties dialog of ChemDraw, benzene ring with an ether, amine or phosphane you specified that the bond type may be single or group, a query might look like the following: double, S/D. Finally, by entering “S,Se,Te” enclosed in brackets, you specified that one of these elements [O,N,P] must match in the target molecules. Searching fullerenes Figure 18.34 Atom list query A search of fullerenes can illustrate the restrictions you can place on a formula search. Suppose you Atom types and bond types want to find all fullerenes containing 20 to 80 car- To broaden or narrow a search query, you can de- bon atoms, but you also do not want to include fine the properties of the atoms and bonds in a large organic molecules. structural query. These properties are definable in The formula query could be: ChemDraw Pro using the Atom Properties and Bond C20-80 H0 Properties dialogs accessible from the Structure By designating zero hydrogen atoms, you exclude menu. See Appendix A, “.” for more information. hydrocarbons from the hit list. By clearly capitaliz- Suppose you want to find all molecules that contain ing the elements and spacing the query, you avoid a non-oxygen chalcogenide bonded to another at- searching ambiguities, although there were no am- om, not necessarily carbon. You also want the bond biguities in this example. type between the chalcogen and the other atom to be a single or double bond. The query, drawn in Searching link nodes and multivalent Rs (MVRs) A link node is a placeholder for zero or more unspecified atoms. It is especially useful when searching for targets with any of several ring sizes, or chains substituted in particular ways at either end. While link nodes are traditionally divalent, Chem- Finder 11.0 places no constraints on the upper limit of the range. Multi-valent R (and A) atoms are func-

ChemFinder & BioViz 369 User Guide tionally similar to link nodes. They may be thought ic would give the following results of as “higher valent” link nodes. :

Query Results Administrator

Will hit

Hits cyclopropanones, Hits alpha, omega- cyclobutanones, and dibromides and ß-lactams bromine

Figure 18.36 Link nodes The traditional representation of a link node is CH2, but this is misleading because any atom type can substitute for the link node. For this reason, Chem- Finder 11.0 represents link nodes as R. R (without Will not hit a repeat count) can match any number of atoms, including zero. Although any atom type of a target atom matches a link node, you can impose two restrictions the on the link node: Figure 18.37 Results of a link node query • Unsaturation • Ring topology. Searching more than one substructure Using ChemDraw's Atom Properties menu to apply A substructure search may contain more than one either of these properties to the link node restricts substructure unit. Suppose you want to find all the range of target atoms to the specified topology. compounds in the CS_Demo database which con- For example, specifying the link node to be aromat- tain a benzene substructure and another substructure unit containing chlorine bonded to any atom. A structure query, as drawn in ChemDraw would look like this:

ACl

Figure 18.38 Structure query with two substructures You should get five hits. Browse the hits. By specifying the query as above, you obtain hits such as benzyl chloride, shown below, where the substruc-

370 ture units are not connected. shown below

. H Cl O Cl O

H Cl OH O

O Figure 18.39 Benzyl chloride, hit by query with two OH substructures The substructure units can overlap; they can share a common atom. Examples of this overlap are Cl Figure 18.40 Overlapping substructures in the hit list

ChemFinder & BioViz 371 User Guide Administrator

372 Chapter 19: Importing and Exporting Data

Overview •Microsoft Word (doc) • TIFF (tif) You can move data into and out of a database if the data is in a supported file format. You can import • Windows metafile (wmf) single files, import or export databases, or add data For information on the .cdx, .ct, and .cdxml file for- to an existing database. mats, see the ChemDraw Users Guide. For informa- Supported file formats tion on the .c3d file format, see the Chem3D User’s Guide. For information on MDL file formats, see ht- ChemFinder 11.0 allows you work with individual tp://www.mdli.com/ (A document describing the file chemical structures and reactions in various file for- formats is available in PDF format.) mats. The supported formats are: Importing data • ChemDraw (cdx) • ChemDraw XML (cdxml) ChemFinder 11.0 allows you to import ChemDraw structures, Structure Data files (SDFiles) and Reac- • Chem3D (c3d) tion Data files (RDFiles) directly into a database. In • Connection Table (ct) addition, you can import text files that are comma • Delimited text (csv, txt) or tab delimited. • MDL Molfile and V3000 (mol) • May be up to 64 characters long. • MDL RXNfile and Rxn V3000 (rxn) • May include any combination of letters, num- • MDL RDFile (rdf) bers, spaces, and special characters except a • MDL SDFile (sdf) period (.), an exclamation point (!), an accent •MDL Sketch (skc) grave (`), or brackets ([ ]). • MDL Graphic (tgf) • Must not begin with leading spaces. •Questel F1D (f1d) • Must not include control characters (ASCII values 0 through 31). •Questel F1Q (f1q) • Must not include a double quotation mark (“) • SMD 4.2 (smd) in table, view, or stored procedure names. Supported formats for output files only: Importing structures •Bitmap (bmp) ChemFinder 11.0 imports structure files directly • ChemFinder 11.0 XML (cfxml) into a database. You can choose to replace the ex- • Encapsulated Postscript (eps) isting records, append new records, or merge the •GIF (gif) data, eliminating duplicates.

ChemFinder & BioViz 373 User Guide The general procedure for importing structures is: 2. Browse to a folder containing structures. 1. Use the File>Import submenu, to choose the type 3. Select a file or files (using Ctrl+click or of structure file to import. Shift+click) and Click the Open button. Administrator The Data Import dialog box appears.

Figure 19.1 The File>Import submenu The Open Chemical Structures dialog box appears.

Figure 19.3 The Data Import dialog box 4. Click the File button, and select a database to import into. TIP: You can also type in a name to create a new database file.

5. Choose the type of import: Overwrite, Append, or Merge. If you have selected Merge, click the Merge tab and choose the matching field, match options, and logging options. Figure 19.2 The Open Structures dialog box 6. Select the fields to be imported with the checkboxes.

374 Optional: Double-click the field name to The structures are imported to the specified change the name of the field, field type, and database. width in the Data Field Import dialog box. Importing structure data and reaction data files ChemFinder 11.0 allows you to import Structure Data files (SDFiles) and Reaction Data files (RD- Files) directly into a database. Because these files contain both structures and data, ChemFinder 11.0 creates fields in the database to accommodate the incoming data.

Figure 19.4 The Data Field Import dialog box In RDFiles, incoming data may be hierarchical and complex. When loading RDFiles, ChemFinder 11.0 7. Optional: Click the Logging tab to change details converts the data to a relational form, creating new of the log file. tables as necessary and generating linking data. 8. Optional: Click the Form Style tab to select the NOTE: When importing RDFiles, boxes are automati- style of boxes that will be created for new fields. cally created on the form only for fields in the root table of the 9. Optional: Click the Advanced tab to set the RDFile. Subforms must be created and positioned manually. Advanced options. If you have a blank form when you import, Chem- • Import only part of a file by setting the start- Finder 11.0 creates boxes on the main form. If you ing point. You may indicate a starting point have a form with boxes when you import, new box- by line number, byte number, or record es are created on tabbed forms. number. You can import with a form linked to a database, a • Select the version of the ChemFinder data- blank form, or no form. If you import with no base to be created. Versions back to 7.0 are form, ChemFinder 11.0 creates a new form. Selec- supported. tions you make on the Form Style tab of the Data • Import structures only by selecting the Import dialog box determine what the form will checkbox. look like. • Enter duplicate reagent values by checking To import structure and reaction data files: the Store redundant reagents checkbox. 1. Use the File>Import submenu, to choose the type NOTE: In SD and RD files, reagents and catalysts of structure file to import. are specified in each record. ChemFinder 11.0 stores The Open dialog box appears. them in subtables. Thus, if the same reagent appears in 2. Choose the file to import and click the Open but- more than one record, ChemFinder 11.0 only needs to ton. store it once. You can over-ride this default with the The Data Import dialog box appears. checkbox. The Import dialog box scans the file to determine 10.When you have finished selecting your options, what data fields are present and how much space to click the Import button. allow for them in the database. The number of records scanned is shown in the status bar. If the input file is large, the scan may take a while.

ChemFinder & BioViz 375 User Guide • Structures registered—logs an entry for each structure stored in the database • Data registered—shows each data item stored

Administrator in the database • Database schema—shows input fields found and columns generated The log file for an RDFile import additionally presents an overview of the data table hierarchy within the RDFile. You can choose whether to create the log file or not. If you choose to create the log file, you can save it with a different name or append to an existing log file. Importing from a specified location You can start an import from an arbitrary location Figure 19.5 Scanning a data file in an SDFile or RDFile, such as a byte or line num- To interrupt the scan: ber. Press the Esc key. To set the location from which to import: A message box appears to confirm that you 1. Click the Advanced tab of the Date Import dialog really want to stop. The scan continues until box. you click Yes. To abort the scan: Click the Stop scanning button. NOTE: You should let the scan go to completion so that all needed fields are created in the database before loading. Using log files During the import, ChemFinder 11.0 creates a log file of the actions taken. The log file (.log) is a text file that is created alongside the input file and over- writes any previous log file. The log records data of your choice form the following options during the import. • Errors—errors and warnings • General data—information about the input file and import process Figure 19.6 Date Import dialog box, Advanced tab • Records processed—logs an entry for each record of the input file

376 2. Select the appropriate options. 11.0 Drag and Drop options.

To start from Click type of file supported comments file types the beginning of the beginning. SDFile or RDFile Structure •CDX Must be dropped into •SKC a structure box. a specified line line and type the line •MOL number number. •MST •WMF a specified byte byte and type the byte Graphic Must be dropped into number number. •EMF a picture box. •BMP a specified record record and type the •GIF record number. •PNG •TIF 3. Click the Import button. •CFW Reading a structure Form Does not need to be dropped onto an In addition to importing, ChemFinder 11.0 can existing form. read files of any of the supported structural formats. For example, if you have structures stored in Multiple files can be dropped at once, but you can- ChemDraw format, you can open them directly from not mix types (as defined in column 1 of the table). ChemFinder 11.0 without having to import or re- If several structure or graphic files are dropped at draw them. once, they are loaded into successive ChemFinder To read a structure from a file into a structure box: 11.0 records. If only one is dropped, you are asked if you wish to append the structure/graphic in a 1. Right-click in the structure box, and click the new record or overwrite the existing record. If more Read Structure context menu command. than five structures/graphics are dropped, an alert The Open dialog box appears. will ask you if you wish to proceed. 2. Choose the file to read. Dropping one or more form files opens the forms, 3. Click the Open button. without affecting the current form and database. The structure is read into the structure box. The database is not affected by this operation Importing text files until you choose Commit Changes or move off You can import comma or tab delimited text files. of the record. The Import Delimited Text command uses the Drag and drop same dialog and has most of the same features as Import SDFile. Delimited text (DT) differs from You can drag certain types of files from the Win- SD files in that: dows Explorer or Desktop onto ChemFinder 11.0. The following table summarizes the ChemFinder • DT files cannot contain structures.

ChemFinder & BioViz 377 User Guide • DT files are not as well defined, and require 7. Go back to step 1 of the import procedure to interpretation in order to determine field begin the import again. names and delimiter type.

Administrator TIP: Once you have specified a delimiter, it will be To import text records into a new database: remembered and you will not have to repeat this 1. Open a new, blank form. operation. 2. Click the File>File Import>Delimited Text menu The input file scan also determines the names and command. types of the data fields in the input file. Field names 3. In the File Open dialog, browse to select the must appear in the first line of the file, in the correct input file. order, separated by the same delimiter as the data The input file is scanned to determine the field items. Field types are determined by examining all delimiter. If the file extension is “.csv,” the the data in each column, using the same rules as for delimiter is taken to be comma. If the exten- SD import: if all items in one column are integers, sion is “.txt,” the first few lines of the file are then the field type is set to integer, and so on. examined for the presence of commas or tabs. Widths of text fields are set to accommodate the If one or the other is found, it is taken as the largest item in the file. delimiter. If not, an alert is presented. This alert will appear in two cases: Exporting data files • The input file contains only a single column. You can create a new SDFile, RDFile, ASCII text, OK The alert can be ignored (click the but- or MS Word file by exporting records from an ex- ton). isting database. Text files can be saved in text (*.txt) • The input file has some delimiter between format, or in the Comma Separated Value (*.csv) fields other than tab or comma. format readable by most spreadsheets. When you In this case you must specify the delimiter export a file, all records in the current hit list are using the File Export dialog box. exported. You can include or exclude fields to be To specify the delimiter using the Role Export dia- exported from a checklist. log box: The Data Export dialog box is similar to the Data Import dialog box. It gives you options for file nam- 1. Click Cancel to dismiss the alert and abort the ing and file type selection, and lets you select which import. fields will be exported. If you save to an existing file, 2. Open a form containing data, and retrieve a you have the option to replace or append the small hit list. records. 3. Click the File>Export>Other menu command. The Text Options tab of the dialog box contains The File Export dialog box appears. options relevant to both text file export and struc- 4. Click the Text Options tab. tured text export. It also has an option (Prefix out- 5. Choose the Other option, and specify a delimiter. put filenames) relevant to Oracle subform data, and 6. Click the Export button to save the choice (and an option to select only the fields on the current tab carry out an export) (for tabbed ChemFinder 11.0 forms).

378 To export a file: 4. Click the Text Options tab and choose appropriate options. 1. Use the File>Export submenu to select the output file type. NOTE: Choosing Comma delimited does not automatically set the file type. Text files (*.txt) may be either tab delimited or comma delimited. If you want to export in the Comma Separated Value (*.csv) format, you must name your file accordingly–either by typing the name or selecting the file type from the Save As dialog box.

5. Click the Export button. The file is exported. Saving structures Saving structures is similar to exporting them, without the fuss. To save the structure on display: 1. Right-click in the structure data box, and click Figure 19.7 The File>Export submenu the Save Structure context menu command. The Data Export dialog box appears. The Save As dialog box appears. 2. Choose the destination directory. 3. Type the file name and choose a file format. 4. Click the Save button. The structure is saved to the indicated file. You can read these files with any application that supports the specified file format. NOTE: To save most of the file types listed above, you must have ChemDraw Pro installed. Using copy-paste with structures You can copy structures and paste them into Chem- Draw or ISIS/Draw. You can also use the Copy As command to copy the structure as a text string. The structure Copy As command has three options. •The Name command invokes the CS Figure 19.8 The Data Export dialog box Struct>Name ™ utility. Struct>Name gener- 2. Type a name and path for the file, or click the ates systematic chemical names with proper File button and browse to an existing file. CIP stereochemistry descriptors. 3. Select/deselect the fields you want to export.

ChemFinder & BioViz 379 User Guide •The SMILES command creates a SMILES 3. Paste the data into the other application using string. A SMILES string is a standard way to Ctrl+V or the Edit>Paste menu command. describe a chemical structure in a line of text. Exporting an ASCII file

Administrator Several software packages use SMILES strings as a way to enter and store chemical structure Delimited text files may be the most universal file information. format used by non-chemical applications. In a de- •The InChI™1 command invokes the Cam- limited text file, each line represents a record, and bridgeSoft implementation of the IUPAC all fields in the record are listed in order from left to InChI™ algorithm. The InChI™ algorithm right, separated by some character such as a tab or takes a chemical structure and converts it into a comma. Individual records are separated by car- an alphanumeric string. A key aspect of the riage returns. ChemFinder 11.0 allows you to in- InChI™ algorithm is that the generated string clude a header line at the start of the file that lists is independent of the way that a structure is the names of all of the fields. It also allows you to drawn, producing a consistent alphanumeric append to, or overwrite, existing text files. representation of different structural represen- You can import a delimited text file saved by Chem- tations of the same structural formula (canoni- Finder 11.0 into many other applications, including calization). spreadsheets and external database systems. Choose the .csv file format to export to spread- All three commands place the data on the Clip- sheets, and the .txt format for general export. board, allowing it to be copied into other applications. NOTE: In delimited text files, structures are automatically exported as SMILES strings. To copy a structure as a name or InChI™ string: 1. Click in the Structure box to select it. Exporting a Word file 2. Right-click, and click the Copy As>Name or Copy The export to MS Word option is similar to the oth- As>InChI submenu command. er export options, however a couple of points are worth noting: • Export to Word is much slower than to other formats. For this reason, you should probably limit the use of this option to relatively short hitlists. • You can speed up the export by not exporting the structure field. • Structures are exported as OLE objects, and can be edited in Word with the ChemDraw Con- trol. • If you should, by accident, begin exporting a large database, you can terminate the export by bringing ChemFinder 11.0 to the front and Figure 19.9 Copy As Name pressing the Esc key.

1. InChI™ is a registered trademark of the International Union of Pure and Applied Chemistry. InChI™ Material in ChemFinder 11.0 is © IUPAC 2008 .

380 Export to SDFile tion desired. Click the OK button when you have finished. When you export to SDFile, you are allowed to export subform fields. Each subform field is exported TIP: Settings in this dialog box affect the Page Setup, to a separate record in the SDFile, but separate sub- so it’s best to start here. form records are concatenated into a single multi- line text block. 4. Click the File>Page Setup menu command. To export subforms: 5. In the Page Setup dialog box, set the margins and units (cm/inch), layout, and other options. 1. Click the File>Export>SDFile menu command. • The Header option prints the file path at the The Data Export dialog box appears. top of the page. 2. Click the Text Options tab, and select the Export • The Footer option prints the date, time and subform data checkbox. record number at the bottom of the page. 3. Return to the Export tab. In the Field column of Click the OK button when you have finished. the Data Fields table, all subform fields now appear with checks in the checkbox next to the field name. Deselect any subform fields you do margins not wish to export (and select those main form fields you do wish to export). 4. Click the Export button. NOTE: Re-importing a file of this type will not regenerate the original database! It will bring back the data, but not in the subtables and subforms you started with. To do this, export to cfxml. When exporting to SDFile, you may append to, or overwrite, existing SD files. This option is only Figure 19.10 Page Setup dialog box. available for SD files and delimited text exports. 6. Click the File>Print Preview menu command to Printing check the settings. You can print out all or part of your database. 7. Click the File>Print menu command or the printer icon on the main tool bar. To print a database: The Print dialog box appears. 1. Before printing, decide if you want to print a 8. Set the print range and number of copies. You table view or a form view. Set ChemFinder 11.0 may also select a different printer than the to the appropriate view. default. 2. Click the File>Print Setup menu command. 3. In the Print Setup dialog box, set the printer, NOTE: ChemFinder 11.0 defaults to printing a paper size (default: US Letter), and page orienta- single page. This is indicated by the option labeled “Selection”. If, for example, you are printing in Form view and you set the layout in Page Setup to three per page, you will print the record selected and the next two records. If your layout is one per page (the default), you

ChemFinder & BioViz 381 User Guide will print only the selected record. Note also that if a Click the OK button when you have finished. subform is selected, the entire record with the subform is printed. Administrator

382 Chapter 20: Relational Data and Subforms

Overview age sizes and prices are entered many times in the subform. Subforms allow you to work with multiple data ta- By linking these two data tables with a linking bles in a relational database. You should be familiar field you can make these tables relational; one with working with ChemFinder 11.0 forms and da- table can interact with the other. The contents tabases before proceeding to subforms. of a linking field are not important, as long as Accessing relational data using they are different for each record in the main form. Various forms of ID numbers are often subforms used as linking fields. As you browse through the main form, corresponding records in the A subform is a special box within a form that be- subform appear. haves like a separate form file. A subform is used to display information stored within a database, but it Creating a subform usually displays data from a different database (or different table within the same database) than the You create a subform, place form objects on it, and main form. A subform is usually linked to the main connect the subform to a database just as you do a form, so that retrieval of data in the main form also regular form. For detailed information on these retrieves related records in the subform. procedures, see “Creating and Editing Forms” on Like other types of boxes, you can move select and page 297. resize a subform on the main form. However, you Subform changes for users of version 8.0 cannot select it by clicking inside it. You must click the title bar. When you click inside a subform, you and earlier you activate the miniature form inside the box and Creating and linking subforms in ChemFinder 11.0 can work within it. was simplified in version 8.5. Users of previous ver- Below are examples of subform use: sions should note the following changes: • You have data that is associated in a • There is now a single dialog box which sets “one-to-many” relationship. For example, you properties of both the subform box and its want to view a chemical structure together with subform. You set all of the details in one place, its physical properties, stored in a separate in a single operation. table. • In the new dialog box, the Database, Table, and • You are running a stockroom and you want to Field tabs reflect the data source of the sub- store package sizes and prices in the same place form, not the parent form. The database tree because they are related. Each chemical may be control in the dialog box also shows subform available in lots of package sizes, and you data source. You can use the Explorer window wouldn’t want to re-draw the structure every to display the tree control of the parent data time you added a new package. You can use a source, if they are different. subform so the physical property information As before, the Form tab shows properties of is entered once in the main form and the pack- the subform, while the Subform tab shows

ChemFinder & BioViz 383 User Guide properties of the box and the linkage between By default, newly created subforms are associated the subform and its parent. with the same database as the main form. • When creating a new subform, you get the To use a different database as the data source for

Administrator same dialog box by clicking within the subform the subform: as by clicking on the box header. 1. Click the Open Database button. • For convenience, the dialog box comes up The Open dialog box appears. automatically whenever you create a new subform box. • After you have created a subform, the subform tool is deselected. This prevents the frequent mistake of drawing a subform box, then trying to draw a data box within it and getting another subform. Creating a subform manually To create a subform: 1. Start ChemFinder 11.0 and open or create a form. Figure 20.2 The Open dialog box The form should have at least one data box, 2. Choose a database and click the Open button. and be linked to an existing database. The Database table appears in the tree control. 2. Click the Subform button on the Form tool- The following illustration shows the CS_Demo database. bar. 3. Click somewhere in the form and drag to create a data box. When you release the mouse button the Sub- form Properties dialog box appears.

Figure 20.3 CS Demo database table 3. Select the table to be linked (in this case, Syn- onyms). 4. Click the Form tab. Select the Generate form check box. If you want to set the style, click the Style Figure 20.1 The Subform Properties dialog box button. See “Creating forms automatically” on page 299 for details on Form style.

384 5. Click the Subform tab. The tab should contain onym field of the Synonyms table of CS_Demo. The reasonable data (Link To SYNONYMS (subform) = subform displays the hits from this search. SYN_ID, Title = Synonyms) based on the choices made so far. Subform generator Introduced in ChemFinder 11.0 10, the Automatic Subform Generation feature enhances the Form Generation feature introduced in ChemFinder 11.0 7, making it possible to create subforms along with standard data boxes. Automatic subform generation is part of automatic form generation (see “Creating forms automatically” on page 299). To generate a subform: 1. Right-click on a blank area of the current form and click the Data Source... context menu com- Figure 20.4 Creating a subform mand. 6. Choose Mol_ID from the Link from MOLTABLE The Form Properties dialog box appears. (main form) drop-down menu. 2. In the Form Properties dialog box, select the Form tab. NOTE: To use the subform relationally to the main form, the two forms must have one field in common. This Linking Field must share the same data type (text, integer, real) as a field in the main form. The fields do not need to have the same name.

7. Modify box properties as desired. You may want to change the box title, font, presence of scrollbars, etc. 8. Click the OK button. The new subform appears Generate form checkbox showing one synonym. and Style button 9. Optional: double-click in the subform to switch it to table view. Figure 20.5 The Generate form checkbox and Style button The Subform is connected to the database you on the Form tab of the Form Properties dialog box chose. 3. Select the Generate form check box, then click the In this example, when a record is retrieved in the Style... button. main form, its Molname is used to search the Syn- The Form Generation dialog box appears.

ChemFinder & BioViz 385 User Guide 4. Click the Subforms button. change the overall layout of an existing subform. To change the layout of an existing subform: 1. Right-click on the title bar of the subform data Administrator box and click the Properties... context menu command. The Box Properties dialog box appears. subforms button 2. In the Box Properties dialog box, select the Form tab. 3. Select the Generate form check box, then click the Style... button. The Form Generation dialog box appears. In Figure 20.6 The Subforms button the left panel, all of the Fields are selected by The Subform Generation dialog box appears. default. 4. Deselect those fields in the Choose fields to be included section that you want to exclude from the form. link to field 5. In the Form style section, select the form options link from field you want. For a detailed description of the options, see “Creating forms automatically” on page 299. Add button 6. Click the OK button. 7. Click the Properties dialog box OK button. A warning dialog box appears allowing you to Figure 20.7 Subform Generation dialog box create a new form or replace the existing form. 5. For each subform you want to include: Click No to create a new form, Yes to replace a. Choose a field in the Link from box to specify the existing form. the linking field of the parent form. b. Expand the table you want to display in the subform in the Link to box, and select the linking field of the subform. c. Click the Add button to append the selected subform to the list being generated. Figure 20.8 Warning message when replacing a form 6. When you have added all subform links, click the The subform is automatically changed. OK button to close the dialog box and return to the Form Generation dialog. Working with subforms Changing the layout of an existing You must select a subform to work with it. The subform title bar is highlighted when the subform is se- subform lected. After a subform is selected, the toolbars You can use the Form Generator to automatically affect the subform. You can use the Record tools to

386 browse the subform and add records. To display a subform in Table view: To select a subform: Select the subform and do one of the following: Click anywhere in the subform. • Double-click on a record in the table. To return to the main form: • Click the View>Data Table>In Current Window menu command. Click the main form. • Type Ctrl+T To select a subform box: With the selection tool, click in the title bar. • Click the Switch to Table tool. A table view of the records in the subform Searching a subform appears. You search a subform the same way you search the To return to the Form view, repeat the above action. main form. You can search a subform and the main Subform plots form simultaneously. To search a subform: A third type of view is the plot view. You can use BioViz to create a 1-D, 2-D, or histogram plot of 1. Click the Search>Enter Query menu command to any numerical field(s) of the data table connected to clear the subform and main form. the subform. TIP: You can also click the Enter Query icon on the To create a subform plot: Search Toolbar or type Ctrl+F. You must be working with a form that has a 2. Enter a query in the subform data box. See subform with at least one column of numeric data. “Database Queries” on page 345 for details on entering queries. 1. Click the subform box to activate it. 3. Click the Search>Find menu command. 2. Click the View>Subform Plot View toggle. If the subform is linked to the main form the The BioViz Plot Properties dialog box hit list contains the main form records related appears. to the matches in the subform search. You can 3. Set up the plot. See “Creating a plot” on page browse and save this hit list just as you would a 397 for more information. hit list from a main form search. NOTE: If the subform is not linked to the main form, it be- For 2-D plots, both numeric fields must be in haves independently of the main form and is the data table associated with the subform data box. searched separately. The plot appears in the subform data box. Viewing subform data in a table Subform plots have less functionality than regular BioViz plots. While mousing over a point will high- If you have more than one record in the subform light it, selection, filtering, and coloring are dis- associated with a single record in the main form, it abled. Since selection is disabled, subform plots are may be more convenient to view the subform as a always in “zoom on drag” mode. table while you browse through the main form. The table view shows you the complete list of related Use Control+W to toggle between the form, table, records for each entry in the main form. and plot views. The Switch to Table tool only toggles between form and table, as does double-clicking in

ChemFinder & BioViz 387 User Guide the subform. To specify a CAL script: TIP: The subform remains selected until you click the main 1. Right-click on the subform header and click the form, so you can only browse in the subform. If a plot is dis- Properties... context menu command. Administrator played, browsing does nothing. The Subform Properties dialog box appears. If you toggle the main form to table view when a subform plot is displayed, the plot is displayed as a graphic rather than an active plot. Using scripts in subforms You can specify a CAL script to be executed when you click an item in a subform in table view. The subform can then be used as a list selection box. The script can use CAL commands to retrieve the Table script box clicked item, and perform an action on it. For more information about CAL, see Appendix E, “CAL Commands” on page 469. Figure 20.9 The Table script box. 2. In the Table script box, type the name of a CAL script or click the Edit button and select a script. 3. Click the OK button. In Table view, the entries are blue and under- lined indicating that they are hot linked to a script. 4. Click any of the hot links to run the script.

388 Chapter 21: Compound Profiles

ChemFinder 11.0 introduces a new feature called adjusted to penalize any deviation from some “ide- Compound Profiles, a way of visually comparing al” range more severely than the corresponding and ranking structures based on values of selected cost function for activity. properties. The default display preference is to have white re- A compound profile is a graph, or, more typically, a gions in the bars represent ideal values, darker re- series of graphs, each of which plots the value of a gions increasing deviation from the ideal. numerical field in the database on a vertical bar col- The normalization function permits properties of or-coded to show regions of “cost”, or undesirabil- different types to be compared. A score, the total ity. These regions are defined by a cost profile deviation from “ideal” of all fields, is displayed. associated with the field. In the profile, costs are Each property can be assigned a weight to adjust its normalized to score between 0 and 1, where the ide- effect on the overall calculation. The score is the al is assigned the value of zero, and the slope of the same for a given compound regardless of whether deviation to maximum (1) is user-defined.1 or not you’ve done a sort, or where the compound appears within a hitlist. A “bad” compound has a high score.

score

Figure 21.2 A compound profile for MW, LogP, and IC50. A compound profile is useful as a visual indication Figure 21.1 IC50 profile. of the “quality” of each compound. As such, it is most useful in table view, where you can see and The cost profile is designed by the user to reflect compare several profiles at once. The highest bene- their opinion of what constitutes a “good value” for fit comes from using profiles in sort/search opera- a property. The user can adjust the cost profile to tions. You can pose one compound as the query, reflect how unhappy they would be when a com- and then sort the remaining ones by deviation from pound deviates from the ideal value by changing the that query. range of values at zero and the slope of the line to one. Creating a compound profile For example, a user might want a drug candidate to have a good solubility (in units of mg/ml) and good Profiles are displayed on the form in a special data biological activity (in units of nm). They might be box, created with the Profile tool. willing to sacrifice some activity to get better solu- To create a Profile box: bility, so the cost function for solubility would be

1. The function is a normalizing linear spline.

ChemFinder & BioViz 389 User Guide The database connected to the form or sub- • You may choose a log scale, if no part of the form you are working with must have at least Value Range is negative. one numeric field. • You may weigh this profile relative to other

Administrator profiles; where 100 is important, 0 is not. 1. Click the Profile tool on the Form toolbar. 4. On the Profile Choose page, choose a cost pro- 2. Drag a box on the form. file. The Profile Wizard appears. Choosing from this gallery is just for convenience. Any pattern you choose can be later modified to any other shape. TIP: As you click each profile, a line of descriptive comments is displayed below the gallery window, to aid your selection.

5. On the Cost Profile page, you may edit your profile. See “To change a cost profile:” on page 391 for details. 6. The Profile page of the wizard has an “add another field” checkbox that changes the Finish Figure 21.3 The Profile Wizard button to a Next button. Click Next to repeat the 3. On the Field page, choose a numeric field from procedure for each profile you want to add. the drop-down menu. When you have added all of your profiles, click the Finish button. The profiles are displayed in the data box. Editing a compound profile You can edit any of the characteristics of a compound profile with the Compound Profile Editor. To edit a profile: Double-click in the profile data box. The Compound Profile Editor appears. To add a new profile: Figure 21.4 The Field page of the Profile Wizard • You may edit the name automatically entered Right-click in the editor window, then click the Add Field context menu command. in the Display As text box. • You may edit the Value Range. To delete a profile: The default display is the actual low/high 1. On the Profile tab, click one of the profiles to values for the first 1000 records in the select it. database. 2. Right-click in the editor window, then click the Remove Field context menu command.

390 To change the order of the profiles: As you drag, the X and Y coordinates of the point are displayed on the grid. 1. On the Profile tab, click one of the profiles to select it. TIP: You cannot drag past a neighboring point. 2. Right-click in the editor window, then click the Move Right context menu com- 3. To add a new inflection point, right click on the mand. line segment where you want the new point, and click the Add point here context menu command. To change the field associated with a profile: 4. To delete a point, right-click on the point and 1. On the Profile tab, click one of the profiles to click the Remove point context menu command. select it. 5. To change the ideal value, drag the pink dashed 2. Click the Field tab. Change the Source with the line on the grid to a new location. drop-down menu. Change any of the other vari- 6. To choose a different template, right-click any- ables as required. where in the editor window, click the Choose con- 3. Click the Cost Profile tab and select a new profile. text menu command, and select a new template. NOTE: You must select a new profile when you change 7. Click the OK button to save changes and exit the the source field. If you forget, you will be prompted with editor, or Cancel to exit without saving. an error message. Display preferences 4. Click the OK button. You can change display characteristics of a profile The cost profile is displayed, and may be with the Profile Display Preferences dialog box. edited. Changes you make apply only to a selected profile 5. Click the OK button to complete the change. box, unless you choose to reset the defaults. To change the profile display preferences: To change a cost profile: 1. Right-click a profile box and click the Compound 1. On the Profile tab, click one of the profiles to Profile > Preferences... context menu command. select it, then click the Cost Profile tab. The Profile Display Preferences dialog box appears. ideal value

Figure 21.5 Cost profile, showing the drag points and ideal value line. Figure 21.6 Profile display preferences 2. To change an inflection point, drag it to a new 2. To change the base color of the cost band location. (default = red), select a primary color in the Cost Shading Color section.

ChemFinder & BioViz 391 User Guide 3. To reverse the “polarity” of the cost band, dese- 3. For easiest comparison, switch to Table View. lect the Ideal = white checkbox. When checked, light shades are “good”, dark are “bad”; when

Administrator unchecked, the reverse is true. 4. To change the color of the value marks and the lines between them, click the Values button and select a color from the color picker. 5. To change the color of range labels, click the Labels color button and select a color from the color picker. score 6. To turn off the range labels (to the right of the dist cost band), deselect the Labels checkbox. 7. To use the current settings as the defaults for all subsequent profile creations, click the Use As Figure 21.7 Profiles in the table view Defaults button. The dist value in the profile (displayed in red at the 8. When you have finished editing the settings, bottom of the chart) changes when you sort. Before click the OK button to save the changes, or Can- sorting, it matches the score value. After sorting, it cel to discard. displays the deviation of that compound from the base. If you sort relative to a compound, then that Search/sort compound gets dist = 0 since it defines the refer- You get the most advantageous use of profiles in ence point. The dist value for other compounds comparing compounds by using the search/sort will increase as they become less similar to the base. function. Select one compound as your base (for You can also sort relative to the ideal value. In this example an “ideal” compound with an overall score case, the dist value for each compound is the same of zero), then sort the database by increasing devia- as its score, and the records are ordered on that ba- tion from that score. sis. To use Search/Sort to compare profiles: TIP: To reset the database, right-click in the Mol_ID field and click the Sort Column>Ascending context menu com- You must be in Form View to begin this proce- mand. dure. 1. Browse to the compound you want to use as Example: your base. Do the following: 2. Right-click in the Profile data box, then click the 1. In the CS Demo database, create a profile with Compound Profile>Search/Sort>Sort relative to cur- one field, Molweight, and a cost profile such that rent context menu command. values below 100 are ideal, and above 100 ChemFinder 11.0 sorts the database. increasingly bad. 2. Browse through the compounds. Benzene (mw 78) falls in the ideal region, so it has a cost of zero and a score of zero. Bucky- ball fullerene (mw 800+) falls way outside the ideal, so it has a high cost and a score of 1.

392 3. Right-click in the profile box. Cost Profile Chooser dialog box was designed to 4. Click the Compound Profile>Search/Sort>Sort rela- help you get started. Some are based on user expe- tive to ideal context menu command. rience, other chosen to provide the most common cost profile patterns. As you work with the com- 5. Click the Switch to Table icon to make it pound profiler, you will develop your own tem- easier to compare the profiles. plates and may want to substitute them in the The compounds are ordered by dist value from chooser. 0.00 to 1.00. Note that the score and dist val- The templates are taken from files stored in the ues are the same. ...\ChemFinder\system\profiles\ folder. The files 6. Browse to bromobenzene (mw 157). have a CPX extension, and the name of each file is The score for this compound is not ideal. It the name given to the template. The Cost Profile will be approximately 0.1, depending on how Chooser displays all files in this directory having the you set the profile. CPX extension. The internal format is XML, readable in Notepad. TIP: You can sort by Molname or MW to find the To remove a template from the chooser, delete the compound more easily. corresponding file, or move it to another location, 7. Click the Switch to Table icon again to return to or change its extension. form view. To add or modify a template: 8. Right-click in the Profile data box, then click the 1. Double-click in the profile data box to open the Compound Profile>Search/Sort>Sort relative to cur- Profile Editor, then click the Cost Profile tab. rent context menu command. 2. Edit the profile until it looks the way you want. 9. Switch back to Table View are browse the 3. Right-click in the edit window, then click the results. Save... context menu command. Bromobenzene is at the top of the list. Other 4. When prompted, enter a line of descriptive com- compounds with similar scores follow. Note ments to be displayed underneath the chooser that the score and dist values are no longer window, and click the OK button. equal. 5. Type the name you want to appear in the Customizing chooser, and click the Save button. The gallery of cost profile templates shown in the

ChemFinder & BioViz 393 User Guide Administrator

394 Chapter 22: Visualizing Data With BioViz

With BioViz , you can identify trends and correla- BioViz Plot Properties dialog box. tions in your data, and within subsets of your data, without the extra step of exporting to another ap- points plication. You can have as many plot windows as legend you like, each showing a different visualization of data from the current form. background color BioViz is designed to be used with the Structure Window and the Queries Tree. While not necessary to creating visualizations, they offer considerable convenience when working with plots. Before axes working with BioViz , go to the View menu and activate the Structure and Explorer windows. The Struc- Figure 22.1 BioViz Properties Display tab ture window gives you a way to display structures without taking up room on the form. The Queries Axes Tree in the Explorer Window gives you an easy way You can now set both the content and the font used to track multiple hitlists. for each axis. The default X and Y labels are the To create a new plot, view an existing plot, or delete names of the fields plotted, but you can now enter a plot, use the BioViz Plots submenu of the View any text in any font to override the default. You may menu. Plots are saved with the form and will come also choose whether or not to display the X and/or back when it is opened, though they may be hidden. Y grids by using the checkbox next to each label. TIP: Labels are “sticky”, that is, the labels used for the Changes in version 11 previous plot are the defaults for the next plot created. If you entered axis labels for Plot 1 and want to use default labels User-customizable styles for Plot 2, you must go to the Display tab to delete the label entries when you create Plot 2. Point shapes Legend You may now select one of six shapes for data points: square, circle, triangle, diamond, cross, or You may add a legend or comments to be displayed star. Selected or moused-over points retain the on the plot. same display as in earlier versions: the selected point 1. Right-click in the plot, then click the Properties... is displayed as a double hollow red circle, and points context menu command. being moused-over (pointed at) are displayed as red The BioViz Plot Properties dialog box appears. solid with a black circle. Point shape selection is from the Display tab of the TIP: You must right-click either in the plot area or in the top border. Clicking any other border brings up different context menus. See “Changing the display” on page 405 for details.

ChemFinder & BioViz 395 User Guide 2. On the Display tab, enter your legend in the Com- omitted (though noted). Version 10 omits both ment text box. You may also enter a font and “empty” X and “empty” Y points. All omitted point size for the legend. points are noted, and may be reviewed by clicking

Administrator 3. Click the OK button to display the legend. the Notes button at the bottom of the chart. The default position for the legend is in the upper right corner of the plot. After you have created it, you may position it where you want by dragging it. To remove the legend, open the BioViz Plot Prop- erties dialog box and delete the text in the Comment box.

Background color Figure 22.2 Plot Notes You may now choose any background color you Selection and mouse-overs want for a chart. A Color...button on the Display tab of the BioViz Plot Properties dialog box opens a To facilitate viewing selected points when queries color picker dialog box. are displayed, the selected point is displayed as a double hollow red circle. Points being moused-over Other changes (pointed at) are displayed as red solid with a black Extended state saving. Filter slider positions and circle. Mousing over a selected point displays a dou- colored-by state of plots are now saved with the ble hollow red circle surrounded by a black circle. form. Points belonging to queries are displayed as solid colored points without circles. Improved Filter display. See “Filtering” on page 402 for details.

Improved statistical display. See “Statistical anal- moused-over point ysis” on page 401 for details. Improved Histogram bar coloring. See “Histo- query point grams” on page 398 for details. selected point

Changes in version 10 Figure 22.3 Point Selection

Removal of empty points Details window In version 9, a point which has an X value, but not The Details Window displays field values (other a Y value, is represented as a so-called “empty” than Structure) when viewing a BioViz plot. To dis- point on the plot with a distinctive marker. If there play the Details window, select it from the View is a Y value, but no X value, the point is simply

396 menu. results of database queries. You can filter the plot to limit the data range within a given dataset. To create a new plot: 1. Click the View>BioViz Plots>New menu command.

Figure 22.4 View menu New Toolbar Options The window floats by default, but can be docked with other windows.

Figure 22.6 New plot menu The BioViz Plot Properties dialog box appears.

Figure 22.5 Details Window To add new fields to the Details Window: 1. Right click in the Details Window. 2. Select the field to be displayed. A check mark appears next to the selected field. Fields display in the order you select them. Figure 22.7 BioViz plot properties 3. To remove a field from the Details Window, 2. Select a Dimension (one or two variables) and a right-click and deselect it. Style (line, scatter, or histogram). 3. Select the variable(s) from the drop-down list(s). Creating a plot 4. Optional: select other options, change the name. To begin working with BioViz , select a set of data 5. Click the OK button to view the plot. to work with. You can plot an entire database or the

ChemFinder & BioViz 397 User Guide The plot appears in a separate window. again. Histograms

Administrator Histogram plots are only available when you select a one-variable plot. When you select a Histogram plot in the BioViz plot properties dialog box, the plotting axis switches to X, and the Bins section becomes available.

Figure 22.8 Displaying the BioViz plot In a 2D plot, you may plot any numeric field on the X axis and any other on the Y. For a 1D plot, you choose only the value to be plotted on the Y axis, where the X axis represents record number. For a Figure 22.10 Histogram selection histogram, choose a single value to be plotted on Each bin in a histogram is labeled with its high-low the X axis, with the frequency plotted on Y. cutoff points. Note also that the data for the bin is Another way to select a field to be a variable, or cre- displayed in the status bar as you mouse over it. ate a 1-D plot is to right-click in a property field and When you overlay queries, the histogram bins dis- select BioViz Plot from the context menu. play the partial membership of the selected queries within the bars of the histogram.

Figure 22.9 Selecting BioViz from the context menu When you right-click in a numeric data box, you may choose that value to be plotted on either axis, or as a 1D plot against record number. In the latter case, the plot appears immediately when you release Figure 22.11 Histogram display with overlaid queries the mouse button. For a 2D plot, you must first select a data box for the other axis. Use the Reset X,Y Plot options command to clear both X and Y settings and start BioViz options are available from the BioViz

398 Properties dialog box and from the context (right- click) menu. Some of the context menu commands Dialog Option Description repeat options in the Properties dialog box. Name BioViz automatically names Dialog Option Description plots with sequential numbers (BioViz 1, etc.) Edit this field if you want to give Dimension Number of variables plotted. your plot a different name. One and two dimensional plots are currently supported. Locked Locks the display. When the display is locked, the following have no effect: Style Currently supported plot styles are Line, Scatter, and • filters Histogram. • changes in the current list Bin By number: Sets up n bins • list coloring evenly spread across the whole range of values. n BioViz Plot Properties must be <=500. dialog box options (except Name) are blocked. The By size: Sets up bins of size Display and Analysis tab n. The number of bins will be options are all blocked, even as many as are necessary to though they are not grayed cover the range. out.

Log scale Select this option to display a Selection and mouse-overs log scale. are not affected.

Base Base of the log scale. You Point limit Sets the maximum number must enter a number, thus of points in the plot. Used to for a base e log scale, you limit the plotting time with would enter 2.718281828. very large datasets.

Table 17 BioViz preferences, General tab Table 17 BioViz preferences, General tab

ChemFinder & BioViz 399 User Guide Menu option Description Dialog Option Description

Administrator Zoom on Drag A toggle which selects the Point shape Selects the point shape – mode of operation when you circle, square, diamond, drag a rectangle on the plot. triangle, cross, or star. If Zoom On Drag is checked, the rectangle defines the area Point size Selects the point size. you want to examine, and Values from 2 - 20 may be releasing the drag will cause dialed in. the plot to zoom in on that area. When unchecked, drag- Comment Text box for a comment ging a rectangle selects the or legend. points within it without changing the scale. You can use zoom to reset the scale Background Selects the background even on locked displays. color of the plot. Unzoom Resets the scale after a zoom, Label Text box for custom label or a series of zooms. for both X and Y axes. Rescale to All Scales the plot so that the Show grid Option to display a grid. Points visible points fill the plot X and Y axes may be window. selected separately. Autoscale Automatically rescales every Font Selects the font. Different time you change the list (that fonts may be used for the is, perform a search, restore a Comment, X and Y axes. list, etc.). Table 18 BioViz options, Display tab Locked Locks the display. See Table 17 for details. Menu option Description Copy Image Copies the plot to the Clip- Properties... Opens the BioViz Properties board, allowing it to be dialog box. pasted into other documents.

Table 19 Context menu options Filter Window Opens a filter window. See “Filtering” on page 402.

Table 19 Context menu options

400 able only when curve fitting is chosen. Menu option Description

Selection to List Creates a hitlist from selected data points. The list is displayed in the Queries Tree and is treated and saved like any other search query.

You cannot use Restore Query on a list selected this R2 is available when curve fitting is selected way, but you can use Restore List to retrieve the records. Figure 22.13 BioViz Analysis Table 19 Context menu options In Version 11, results of descriptive statistics are displayed on the plot. Statistical analysis You can perform statistical analysis on BioViz plots. When you specify two variables, a third tab appears on the BioViz Properties dialog box. Version 10 Plot

descriptive statistics display

Version 11 Plot

Figure 22.12 The Analysis tab appears when two variables are specified. For descriptive statistics, minimum, maximum, mean, median, and standard deviation can be calculated for both X and Y variables. R-Squared is avail- Figure 22.14 Displaying Statistical Analysis Results You may choose from linear, quadratic, or cubic curve fitting. A confidence interval of one to three standard deviations may also be displayed. Both descriptive statistics and the curve fit update dynami-

ChemFinder & BioViz 401 User Guide cally when the recordset changes or filters are • All plots associated with a given form are applied. affected, unless the plot is locked before applying the filter.

Administrator Cleaning up the plot–sorting and • Points missing a value for a given field are hid- filtering den whenever the filter for that field is visible. In Version 11, a new design makes filters easier to Once you have created a plot, you might want to read. The range is displayed in black below the slid- clean up the display. There are two ways to do this: er, and the set points in red above the slider. Filter sorting the data on a field, and using filters. name is centered, rather than on the right. Opera- The standard ChemFinder 11.0 sort feature is the tion of the sliders is unchanged. first step in cleaning up a graph. You may sort into ascending or descending order. There are two ways to sort a dataset on a given field: • Right-click in the field box and click the Sort context menu command. • Display the Data table view, and double-click on the table header of the field you want to sort. Filtering BioViz filters limit the display of a variable by trim- ming either end of the range, that is, you can elimi- nate high points, low points, or both from the display. Filters can be set for either or both plotted variables. You may also filter the dataset on other variables, up to a total of 31 filters per chart.

Figure 22.16 Filter window, stacked with details and structure windows To activate a filter: New filter style Old filter style Right-click in the Filter window, and select a vari- Figure 22.15 Filter sliders able from the list. When you view the context Filters are set in the filter window. If the window is not visible, check the box next to Filter Window on the View menu. When a filter is set:

402 menu again, the variable will appear with a check In the bottom diagram, the plot is limited to mark next to it. Molar_Refractivity from 10 to 33. In ChemFinder 11.0 10, histogram plots also re- spond to filtering.

Figure 22.17 Selecting a variable from the list To remove a filter: Figure 22.19 Histogram Filtering Right-click in the Filter window to display the context menu, then click the variable to deselect Filter slider adjustment it. Once the top and/or bottom of the range has been The following bio-assay example shows two plots set, you can move the entire range. For example, in of the octanol/water partition coefficient (CLogP) Figure 22.20A, the Boiling Point filter has been set plotted against an activity measure called to display a range of about 250° —from 501.3°K to Fold_Above_Control. The second is filtered on 753°K. molar refractivity. Note that the upper chart has been locked to prevent the filter from affecting it. A

Figure 22.20 Filter Slider Adjustments By dragging the blue part of the slider, you can view any 250° range of the chart that you want. In Figure 22.20B, the range being displayed has been lock moved to 651.5°K—903.2°K. The size of the range hasn’t changed, just its location. Plotting queries Figure 22.18 Locking a chart When you perform queries (see “Database Que- To apply the filter: ries” on page 345), and have one or more hitlists attached to your form, the BioViz plot displays the Press the thumb at one end of the slider and results of the current hitlist. You can display over- drag along the slider. lays by selecting hitlists rather than making them

ChemFinder & BioViz 403 User Guide current. 3. Click the query to select it for display, over the For example, shows results of a screening test rela- current list. tive to a control. Administrator

Selected query shows a check mark ( b )

Figure 22.21 Screening test results Figure 22.22 : Using overlays To remove outliers more than 2.5SD from the con- Selecting a list by single-clicking in the queries tree trol: (or choosing Color On Plot from the tree context Search for “<2.5 and >-2.5” in the SDs Above menu) causes points on the plot to be recolored. Control field. The recolored points are those which are on both the selected list and the plotted one. You may color The plot displays the results for the hitlist. more than one list at a time. When a list is colored NOTE: By default, the hits are shown on the same on the plot, its item in the queries tree is shown with scale as the original list, which may cause them to cluster a check mark; clicking it a second time uncolors it in one sector of the window. If this happens, right-click and removes the check mark. the plot and choose Rescale to All Points or Auto- Synchronization of plots scale. Rescale to All Points operates on the current datapoints only; Auto-scale sets a switch so that all Multiple plots attached to a form are synchronized. subsequent searches and list operations will If you select (mouse over) a point in one plot, the automatically rescale the plot. same point is highlighted in all other plots (and the related structure is displayed in the Structure Win- To display the results of an overlay on the full list: dow). 1. Open the Queries pane of the Explorer Window. This behavior is slightly modified if one of the plots 2. Double-click on the Full List to make it the cur- is a histogram. You must select (not mouse over) a rent list. histogram bar to highlight points in other plots. Mousing over a point in a line or scatter plot will highlight the point in the center of the correspond-

404 ing histogram bar. b. Drag a rectangle across a portion of the plot.

Figure 22.24 Zoom - dragging the rectangle Figure 22.23 Synchronized histogram This time, when you release the mouse Changing the display button, the plot display zooms in to show only the points selected. When the plot is Once you have selected data points and produced a zoomed, scrollbars appear. Use these to plot, there are several options for modifying the dis- reposition your view of the zoomed plot. play. Click the “circled-point” icon on a scrollbar • Changing Colors–to change the color of a to restore that axis to the previous zoom plot: a. Open the Queries pane of the Explorer window. circle-point icons b. Right-click a list and click the Change Color... context menu command. c. Select a new color from the color menu. • Selection and Zooming–to select a part of the plot and zoom in:

To select part of the plot: Figure 22.25 Zoom results a. Drag a rectangle across a portion of the plot. Right-click and click the Unzoom context The portion of the plot is displayed in red. menu command to restore to the full view. b. To select more than one section, use • Changing the Style–you can change the style Shift+drag or Ctrl+drag. of an existing plot. For example, you can turn a To zoom-in on part of the plot: scatter plot into a histogram. a. Right-click in the plot and click the Zoom on a. Right-click in the plot and click the Proper- Drag context menu command. This is a tog- ties... context menu command. gle switch–choose it again to deselect. b. In the properties dialog box, select the style and click the OK button. The plot displays in the new style.

ChemFinder & BioViz 405 User Guide • Changing Fields—you can change the field c. Select a different field to plot on that axis. plotted on the X or Y axis with the context menu.

Administrator a. Point in the area of the numbers just below or to the left of an axis. b. Right-click. The context menu displays a list of plottable fields.

Figure 22.26 Changing Fields with the Context Menu NOTE: You can only change fields when the chart is not locked. In Data Table display, you can display a substructure search as table of R-group substituents.

406 Chapter 23: ChemFinder/Oracle

Overview • To improve performance, you can create indexes on selected columns. Users familiar with ChemFinder 11.0 will find that, for the most part, ChemFinder/Oracle operates the Other more subtle differences are noted in the sec- same way. You should be able to open a database, tions below. browse, search, register, load and so forth, without worrying about what sort of database is on the back What’s new in ChemFinder 11.0? end. In practice, however, there are several visible Speed improvements in Oracle searching. differences and a lot of invisible ones. Structure search speed has improved in ChemFind- When you open an Oracle database in ChemFind- er. The improvement comes from two factors: im- er/Oracle, you enter a new body of code which provement of the SQL so that hits are added much connects directly to Oracle, and carries out all faster to the hitlist table, and an optimization of cer- searches and transactions on the server. This new tain frequent operations and improved screening mode of operation requires a different underlying efficiency that improves structure search speed in technology, based on Microsoft ActiveX Data Ob- all CambridgeSoft products. jects, and a different philosophy in some aspects of usage, such as the handling of lists, and new fea- New Oracle sort table. A new ChemFinder 11.0 tures, such as index management. All of these are system table is required for carrying out various described in this document. new sort operations. See “Sorting” on page 409 for In ChemFinder/Oracle: information on how to set up the new table. • Searches are carried out on the server, includ- Setup ing structure searches. Before you can make use of the ChemFinder/Ora- • Search results are automatically deposited cle, your machine must be configured as an Oracle directly into tables in the Oracle database. client. If you are already a user of the CS Oracle • Hitlists are not saved in files, but to other tables Cartridge, you are probably all set. If not, you will in Oracle. need to enlist the help of an Oracle administrator to • Saved lists can be annotated, and on restore can set up the server and set you up as a client. be selected from a pick-list directory. For ChemFinder 11.0 installation instructions, see • When working with large databases, you can the readme.txt included on the distribution media. choose a new mechanism which eliminates cer- Ideally, ChemFinder/Oracle should access any ex- tain slow operations associated with large isting Oracle database in any format. In practice, record sets (e.g., Move Last). This is a user there are some limitations. See “Pre-setup proce- choice because there are trade-offs involved. dures” on page 481 for notes and recommenda- • You cannot create an Oracle database, but if tions about preparing an Oracle database for use you have the privileges you can create a table with ChemFinder/Oracle. within one. This causes import operations to work somewhat differently.

ChemFinder & BioViz 407 User Guide Opening an Oracle database The database is opened and the list of tables displayed. To open an Oracle database: NOTE: The list of tables shown in the tree consists of Administrator 1. Right-click in the form and click the Data all tables and views owned by the current user, plus Source... context menu command to open the those to which the user has been granted certain Database tab of the Box Properties dialog box. privileges. To see the details, you can turn on SQL 2. Click the Oracle Database button. tracing while a database is being opened. The CS Oracle Connection dialog opens. 4. Proceed as you would for any ChemFinder 11.0 database: click to select the table you want to display, set other desired options, and check the box on the Form tab if you want to generate a form automatically. Notice the new Oracle tab of the dialog, described in “Setting Oracle preferences” on Oracle page 411 The features on this tab are mainly Database for advanced users and do not require adjust- button ment.

Figure 23.1 Oracle connection dialog NOTE: The Oracle tab appears in the Properties dialog only when an Oracle database is open. NOTE: The Oracle Database button is available to any user. There is no check to see whether the machine 5. Click the OK button. is a valid Oracle client. The database opens, in a display form if you requested one. 3. Enter values for Host name, User name, and Pass- The Database Wizard can also be used to open an word — the same values you use to log in from Oracle database. A button on the Wizard labeled CS any Oracle client. OR: Oracle Cartridge brings up the appropriate Oracle Choose a name from the drop-down list of parts of the process. recently-used items. When you choose an item from this list, it automatically fills in the user When you have opened an Oracle database, note that some Properties dialog tabs show entries not name, and the password if Save password was checked when the item was created. available in ChemFinder 11.0, including: • Database tab: CS Oracle Cartridge version if any. NOTE: The first time you bring up the Oracle Connection dialog box there is no list of recent items, so • Table tab: Table owner name; name of primary ChemFinder 11.0 offers to create one for you. If you index if any. accept, it generates a list of all available hosts, as found • Field tab: Oracle native data type name; name in the file tnsnames.ora created during Oracle client of associated index if any. configuration. When you open an Oracle database and select a table, ChemFinder/Oracle gathers information about the columns. If you open a table you know to contain structures, and ChemFinder/Oracle does

408 not show a structure (or formula or molweight) col- 2. The query is converted to a SQL select state- umn, then it may be necessary to set up some con- ment. Query components in form boxes are figuration information about the table. For details, ANDed together (just as in ChemFinder 11.0), see “Configuration via CF_SETTINGS table” on where the structural parts are calls into the CS page 482. Oracle Cartridge structure search functions. 3. The hits table is created, if it does not already Searching exist. From the user's point of view, searching in Chem- 4. A unique ID is assigned to the new list which Finder/Oracle works basically the same way as in will result from the search. ChemFinder 11.0: you enter a query, search, then 5. The select statement is wrapped in a larger SQL work with the hitlist. Internally, however, the statement which will cause the results to be ChemFinder/Oracle machinery is quite different. deposited directly into the hits table. There are three types of table involved in handling 6. The SQL is executed. hit lists. All are created in your own tablespace. One 7. When the search is complete, the results are new is global, applying to all lists saved from any table; rows in the hits table. Each row contains the new others are connected to the particular table or view list ID alongside the ID of a record from the being searched. searched table. • CF_HITLISTS. The directory of all saved 8. The final list is prepared by a join, selecting rows lists. This table is created the first time any list from the main table which have record ID's is saved. matching those of the new list in the hits table. • SAVED_tablename: All lists which have been The resulting list is ready to browse, save, explicitly saved from a given table or view. This export, etc. is created the first time a list is saved. NOTE: Text searches in Oracle are case sensitive. You will get different hits from the query “benz*” than from • HITS_tablename: All lists automatically saved “Benz*.” after every search over a given table or view. This table is created the first time a search or Sorting list operation is carried out and is deleted at the end of the session. Certain sort operations require a ChemFinder 11.0 Here's what happens when you present a query to system table, CF$_SORT, that may not exist in your ChemFinder/Oracle: current form. If the table does not exist, you will be alerted the first time you attempt such a search in an 1. If the query contains a structure, it is converted Oracle database. to a text representation and copied to a tempo- To create the CF$_SORT table: rary table. 1. Open a new form, then click the File>Database NOTE: The table is called temp_queries. It is menu command. created in the CSCartridge tablespace, and removed as The Form Properties dialog box opens. soon as the search is finished or interrupted. ChemFinder 11.0 does not yet handle the case of 2. On the Database tab, click the Oracle Database... multiple structure boxes where more than one contains button. a query.

ChemFinder & BioViz 409 User Guide 3. Log in as the owner of the schema where your 3. In the right-hand box, right-click the Fxn column ChemFinder 11.0 system tables are located. Typ- and choose a function from the popup menu: ically this will be CHEMFINDER MIN, MAX, AVG, or SUM.

Administrator 4. Click the OK button. NOTE: If you do not have privileges to log in as this user, consult a system administrator. The hitlist is sorted by the selected value(s). NOTE: AVG and SUM are available only for numeric 4. Click the Oracle tab of the dialog box, then click fields; MIN and MAX can also be used for text fields. the Prepare Schema button. ChemFinder 11.0 will create the one new table Handling lists needed, without modifying any of the others. There are differences between ChemFinder 11.0 NOTE: If this button is dimmed, it means you are not and ChemFinder/Oracle in working with hitlists: logged in as the owner of the current schema. • Save List does not bring up a file dialog in 5. Go back to your original form and repeat the ChemFinder/Oracle; instead, it presents a dia- sort. log in which you enter a name and a line of comments for each list. TIP: You may have to click Refresh Session Data on • Restore List presents a dialog in which you the Oracle tab before the sort will work. choose from the available saved lists (see screen shot below); double-click to select one. Sorting by subform value aggregate • Restore Previous List is no longer dimmed after you have done a single search; it is available, In an Oracle database, ChemFinder 11.0 11 allows and will return you to the full list. (This is true sorting the main list over subform field aggregate also in ChemFinder 11.0.) values. If, for example, you have a subform showing a column of test values where there are multiple records in the subform for each main record, you can sort the main hitlist based on the sum or average of the set of test values for each record. To sort by aggregate: 1. Click the Record>Sort menu command to bring up the Sort Multiple dialog box. Figure 23.2 Restoring an Oracle list 2. Click a subform value in the left-hand box to sort by. • Over Current List, Omit From List, and Find List work as before.

410 Setting Oracle preferences • SQL Trace to file. Check this box to generate a text file of the SQL being sent from Chem- When you are working with an Oracle database, the Finder 11.0 to Oracle. To specify an output file, Properties dialog contains a tab for Oracle settings. enter a pathname or use the browse but- Items currently in this tab are as follows: ton. The file is never overwritten: new data are Oracle always appended. Tracing begins when this box tab is checked, and ends when it is unchecked. If you exit ChemFinder 11.0 with tracing in effect, it will be in effect the next time you start up, and you will be given a quick warning about it on the status bar.

CAUTION: The trace file can become very large if you turn on this feature and forget about it.

Figure 23.3 Oracle tab on ChemFinder Preferences • Auto-sort on. Displays the default sort field. Updating and adding data All lists will be sorted in ascending order over If you have privileges to add, update, and delete in this field if no other sort criterion has been the table connected to your form, then you should specified. At present, the auto-sort field is be able to do these operations on records in the da- always the primary key, and cannot be changed. tabase just as in ChemFinder 11.0. However, there • Primary key. Names the primary key of the are some cautions: current table, if any. • Do not modify data in an existing Web Server, • Saved hits. Displays the name of the table in RegDB, or E-Notebook database. Chem- which saved hitlists are stored for the current Finder/Oracle does not automatically prevent form, if one has been created. you from doing this, but you are sure to foul up • Records per retrieve. Sets the size of the those systems unless you go through their nor- ADO recordset cache, that is, the number of mal registration procedures, or know exactly records brought to the client for each retrieve what you're doing. operation. This value can be adjusted for better Most database alterations are possible, as in Chem- performance, but in practice it does not have Finder 11.0: you can add, modify, and delete tables much effect. and fields, assuming you have the appropriate privileges. Differences include: • Cache ID's for faster moves. Checking this box enables a new record-retrieval scheme • When you create a structure field, you can give designed for more efficient browsing of large it any name you like. lists; details are given in “Fast-move caching • Structure columns in tables managed by the CS scheme” on page 481. The state of this check- Oracle Cartridge can be in any of several for- box is saved with the formfile. Currently, when mats, but ChemFinder/Oracle does not allow you check or uncheck this box, you must save and you to choose one: it defaults to a character reopen the form before proceeding. (CLOB) column storing text-encoded CDX.

ChemFinder & BioViz 411 User Guide • ChemFinder/Oracle does not allow you to cre- The Data Import dialog appears: ate an Oracle database in the same way Chem- Finder 11.0 creates an Access MDB file. The Import tab

Administrator equivalent in ChemFinder/Oracle is to create a Output database table. text box Loading You can build ChemFinder/Oracle databases by loading from SDFiles or using Import Structures. (RDFiles should work also, but have not been tested.) However, because you cannot actually create a new database, the procedure is somewhat different from ChemFinder 11.0. You must already have a Figure 23.4 The Data Import dialog box database open, and then you can import to an exist- 4. In the Output database box, you see the name of ing table or have a new one created. the database followed by the table name in To import data and structures into a new table: brackets. To specify the table to load, edit the table name by typing between the brackets. If you want 1. On an empty form, right-click and choose Data to create a new table, enter the name you wish to Source.... give it. If you want to append to an existing table, 1. Click Oracle Database and proceed as described enter its name. under “Opening an Oracle database” on page 5. Set other options as desired, and click Import to 408. It doesn't matter what table you select, since begin the process. you will be creating a new one. TIP: for text fields being imported, make them wider 2. Click the OK button to return to the blank form. than the value determined by the input scan. (To do this, You are now ready to import. double-click the name under Input Field and enter a NOTE: When you click the OK button to dismiss the larger Width value.) Otherwise you might have properties dialog, you will get a warning if the selected problems if you append more records later. table does not have a primary key defined. You can 6. After importing, you should create a primary key ignore this if you are about to create or load a new table. and index; see “Indexing” on page 412. Otherwise, you should consider using an Oracle tool to define a primary key for the table. To append to an existing table follow the procedure above except: 3. Choose Import SDFile or Import Structures and select the source file(s). • Step 1: You can start with an existing form instead of a blank one • Step 2: You should select the target table. When you do, there will be no need to edit the table name in Step 5. Indexing As every Oracle administrator knows, a key to good

412 performance is to index certain columns so that If the selected field is indexed, the index name searches over them become fast lookups. If you in- is shown in the properties box. In the example tend to create, load, or manage tables, then you are below, the index is named IX50. an administrator, and need to know something about indexing. ChemFinder/Oracle provides a Field few tools to assist you. tab There are two types of index of interest to ChemFinder/Oracle: Index Name • Structure indexes. Any column containing structures should have an index created by the CS Oracle Cartridge. If there is no index, searching is still possible, but very slow. • Primary keys. A table containing a column of structures should also have a column of unique record identifiers for use in various list-handling operations. Preferably this column is of Figure 23.5 Locating the index name in the Field tab type INTEGER and is designated as the primary NOTE: If there is no index, or the field is not key of the table. indexable, the Index line does not appear in the list. ChemFinder 11.0 provides information about these indexes, and allows you to create or recreate them if 3. If there is no index, click Create Index. necessary. NOTE: If this button does not appear, it means the To create a structure index: selected field is not a candidate for indexing. 1. Right-click on the structure box of an Oracle- 4. In the Create Index dialog, provide a name for the connected form, and choose Properties.... new index and click the OK button. 2. Go to the Field tab of the dialog. The index is created. You will get an error message from Oracle if: • You provide an index name which is already in use, OR... • The column already has an index. ChemFinder/Oracle does not provide a direct way to delete or overwrite an index, but the CAL SQL command can be used for this purpose. To create a primary key index: The process is the same as for a structure index, except that you carry it out on a field of type Long. This creates an index on the field and also designates it as the primary key. It will fail unless

ChemFinder & BioViz 413 User Guide the column already contains unique, non-null • CURR_TABLE variable. This variable con- values. tains the name of the table connected to the current form. This works whether or not you NOTE: A new button, Set As Structure, may appear

Administrator are in Oracle. if you have selected a certain type of column. This is an advanced feature described in “Configuration via Example: CF_SETTINGS table” on page 482. MSG Current table is $CURR_TABLE TIP: If you want to create a primary key, but don't • OPENDB allows change of table. Normally have a column of unique integer values, you can create this command takes the name of a database, one using a CAL script. For example (assuming you've followed optionally by the name of a table in already created a column and form box called “ID”): angle brackets. In ChemFinder 11.0, it can now take just the table name, and causes the form to loop become attached to a different table in the cur- putdata ID $index rent database — as if you had brought up Prop- record commit erties and clicked a different table name. record next Example: endloop OPENDB CAL causes the current form to be connected to the table CHEM_STRUCTS. Some new features have been introduced into • STATMSG command displays a message on ChemFinder 11.0 Automation Language (CAL) to the status bar. Format: STATMSG . support Oracle. Some are not specific to Oracle, but of general utility: Example: STATMSG • SQL command. When you are connected to an Search is now in Oracle database, you can pass any SQL com- progress... mand which does not return records. The for- • SEARCH SAVE LIST, RESTORE LIST mat is simply SQL where the work with Oracle. Normally you can follow command is not quoted. either of these commands with the name of a Example: file; in ChemFinder/Oracle you can instead provide a list name. SQL create table mytable (id integer).

414 Chapter 24: Using ChemFinder 11.0 with BioSAR

Getting started 3. At the Oracle login, provide your user name and password. This section explains how to export a data form from BioSAR and view it as an equivalent form in NOTE: If you don’t want to view the form now, simply ChemFinder. Once in ChemFinder, you can man- save the file. You can open the file in ChemFinder at age the form using a variety of features. any time. Starting the BioSAR browser ChemFinder file types: bsbxml and cfx To use BioSAR, you must have Internet Explorer 5.5 (with SP2) or greater installed. Whenever you export a data form, BioSAR creates a file with the extension .bsbxml. ChemFinder To start BioSAR: reads this file, and opens the form, linking it directly 1. In Internet Explorer, log into the ChemOffice into the database. Enterprise portal. The .bsbxml file is read-only. Although Chemfinder 2. In the Enterprise screen, under BioSAR Enter- doesn’t allow you to modify the .bsbxml file itself, prise, open a query form using either of these you can still edit the form and save your changes. links: When saved, the form file is assigned the Chem- •Open Form Finder extension cfx. Unlike .bsbxml files, cfx files are not read-only. You can open any cfx file in • Manage your forms ChemFinder, edit it, and save it again. Meanwhile, Performing searches in BioSAR the .bsbxml file is still available whenever you need to open the original form. Before exporting a BioSAR data form to Chem- Finder, you need to search on the data in the Bio- Setting “save password” SAR database. If an Oracle-connected form contains an invalid (or 1. In BioSAR, open a query form of your choosing. blank or no) password, the program prompts you 2. In the form, enter your search criteria and click for a name and password on opening the form. The the Search button. same is true if the Save password box has not been checked in the form properties dialog. This is now Exporting the data form to ChemFinder the default when a form comes from BioSAR. You are prompted for username and password ev- After the search is complete, you are ready to ex- ery time, until you check the Save password box and port the data form to ChemFinder. save the form. To export the form: 1. Click the Display In BioViz button. If the but- Subforms and autolinks ton is not visible, you may need to edit the Bio- When you create a form in BioSAR, you select from SAR form properties. See your administrator. the database which fields you want to include in the 2. When prompted to either save the form file or form. Those same fields appear in the form when open it, select Open. ChemFinder will launch. you import it into ChemFinder. After you import your form, you can continue to build on it in Chem-

ChemFinder & BioViz 415 User Guide Finder using additional fields. The fields you use name in the right pane and click Descending in can also include child tables and their fields. Child the pop-up menu. To remove a field, right-click tables that you add appear as subforms; fields from the field and select Remove.

Administrator child tables are displayed as autolink boxes. 4. Click OK when finished. To add a subform: Sorting by subform fields 1. In the Explorer Window, select the BioSAR tab. One of the new features in ChemFinder 10.0.1 en- 2. Select a child table from the Child Tables direc- ables you to use subform fields to sort data in the tory. main form. Just as in the main form, you select in 3. Double-click the child table. The child table the subform the fields you want and the order you appears in the form as a subform. want them to be sorted (Figure 24.1). You also indicate which value in each field you want ChemFinder NOTE: Not all fields in the child table are necessarily to sort by–the minimum value, the maximum, aver- displayed in the subform. The subform fields are limited age of the values, or the sum. to the same fields you selected in BioSAR and defined in the default form group.

To add an autolink box: 1. Select a child table from the Child Tables directory 2. In the child table, double-click an individual field. The child table field appears in the form as an autolink box.

Multiple sort Figure 24.1 The Sort Multiple field with three of the subform fields selected. ChemFinder’s multiple sort feature lets you rearrange the hitlist based on one or more form fields To sort the main form using subform fields: you specify. For example, you can first sort the list 1. Click the Record>Sort... menu command. by Reg number and then further arrange the list in 2. In the Sort Multiple window, select from the order of Full reg number. left pane the subform field by which you want to Sorting by main form fields sort the hitlist. The subform field is displayed in the format: To sort the hitlist using fields in the main form: subform name: field name 1. Click the Record>Sort... menu command. To sort the hitlist by more than one field, select The Sort Multiple window appears. the fields in order of priority. 2. In the Sort Multiple window, select from the 3. To reverse the order in which values will be left pane the field by which you want to sort. To sorted, right-click the field name in the right sort by multiple fields, select the fields in the pane and select Descending in the pop-up menu. order you want to sort. 4. Also in the pop-up menu, select the value in the 3. By default, each field is sorted in ascending field you want ChemFinder to sort by–max, min, order. To reverse the order, right-click the field average, or sum. The default is Min.

416 5. Click OK when finished. A query labeled Q1 appears as a child of the Full List. Working with query hitlists The Queries tab in the Explorer window maintains a list of search queries from the current and previous sessions. Queries are associated with forms. So, the query hitlist is saved when you save the form. Viewing the query list When you open an existing form, the tree updates to show only the queries for that form. The Explorer Window must be visible to view the Queries control. If it isn’t visible, do the following: 1. Click the View>Explorer Window menu command. 2. Click the Queries tab to display the Queries tree. Query list operations Each time you perform a search or list operation, a Figure 24.2 The Queries control after a typical search new query is generated in the tree. ChemFinder assigns a name to the query and displays it in the tree along with the size of the list (number of hits) and a Changing the query name brief description. The generated name is Q*, If you want, you can change the name of a query to where n is a sequential number and * indicates that one that is more descriptive. Renaming a query also the query has not been renamed or marked for sav- ensures that the query is saved with the form. (De- ing. (See “Saving query lists” on page 419.) pending on your Preferences settings, queries not To perform list operations, begin by performing a renamed may be automatically discarded when you simple search. For example, you can search the da- save the form). tabase for all compounds that have a molecular To rename a query: weight less than 250g/mol: 1. Point to the query and right-click. 1. Click the Enter Query icon ( ) on the Search The context menu is displayed. toolbar or menu. The form goes into query 2. Click Rename on the context menu. mode. The name (Q1) is highlighted. 2. Enter <250 in the MolWeight field of the query 3. Enter a new name and press the Enter key. form and click the Search button. Changing the display color The color of the box next to the query name is the same color to be used to display the points should you plot the results. You may change any query to any color so that the plots look the way you want.

ChemFinder & BioViz 417 User Guide To change the display color: it. 1. Point to the query and right-click. The context menu is displayed. Administrator 2. Click Change Color on the context menu. The color picker context menu appears. 3. Select a new color and click the OK button. The color in the box changes. If you have plotted data with BioViz, you will see that the points that correspond to the query also change color. Child lists You can add a new query either by searching the Full List or searching another query. When you create a new query from another one, the result is a child list. For comparison purposes, it is often an advantage to create multiple child lists, each from a single search attribute, rather than one child list based on multiple attributes. You can create a child list for only the currently se- Figure 24.3 Search menu lected list. If you are not sure that the list you want is selected, double-click it. You are now ready to create a child list query. The following sample procedure describes how to create Before you create a child list, select Over Current List a child list by searching for carboxyl structures: on the Search menu (Figure 24.3). Note that, once selected, Over Current List has a check mark next to 1. Click the Query icon to put the form in query mode. 2. Double-click in the Structure window. The ChemDraw toolbar appears. 3. Using the bond tool, create a carboxyl structure. 4. When you have finished creating the structure, click outside the Structure window. 5. Click the Search button.

418 The new list is created as a child of the previous list. You can verify that you have selected the parent list by viewing the status bar information (Figure 24.6). With the parent list selected, you can add another child list to your query.

Figure 24.6 The value “1187” in the status bar indicates that the parent list in figure 5 has been selected. “38547” is the number of entries in the full list. Merging lists with drag-and-drop In some situations you might want to merge two lists using drag-and-drop. The result is a new list that has attributes based on the merged lists. 1. Select a list and drag it onto another list. The Restore/Merge List dialog opens. Figure 24.4 In this example, Q1 is a child list of a parent 2. Select the type of merge you want (Figure 24.7). list named MW Filter. 3. Click the OK button. A new list is displayed with the merged criteria you selected. Creating multiple child lists You can run similar queries, each with different attributes and displayed as a child of the parent query (Figure 24.5).

Figure 24.7 Restore/Merge List dialog

Saving query lists Figure 24.5 Several child lists of the parent list MW Filter. To create another child list, you must first select the When you transfer data to ChemFinder 11.0 from parent list. To select the parent, do either of the fol- BioSAR Browser, ChemFinder 11.0 opens a file of lowing: type .bsbxml and creates a form to simulate the Bio- SAR setup. At the same time, it restores whatever • Double-click the parent list hitlist was in effect in BioSAR. In ChemFinder 11.0, • With a child list selected, click Restore Previous the BioSAR hitlist is automatically saved when you List on the Search menu or toolbar. save, close and reopen a file. This is different from the default in previous versions.

ChemFinder & BioViz 419 User Guide Working with domains Access database rules

The Domain feature in ChemFinder allows you to • May be up to 64 characters long. create a subset of a database. Once created, a do- Administrator • May include any combination of letters, num- main acts as if it is a full database. Any database bers, spaces, and special characters except a searches you perform are limited to only the do- period (.), an exclamation point (!), an accent main. Any hitlists you create will be added to the grave (`), or brackets ([ ]). query tree as if you are working with the full database. • Must not begin with leading spaces. • Must not include control characters (ASCII val- Creating a domain ues 0 through 31). Before you create a domain, you must run a query • Must not include a double quotation mark (“) to define the subset of the database with which you in table, view, or stored procedure names. want to work. This subset becomes the domain. Creating a local copy of a database TIP: If you want your domain to have a particular order, sort before creating the domain. The order will be preserved If you frequently use a set of data that never chang- for all subsequent use. es, consider exporting the data as a local ChemFind- To create a domain: er database. Having a local database often makes many common tasks run faster; tasks such as 1. Select a query by double clicking on it. browsing, searching, plotting, and analyzing. 2. Click the Search>Domain>Set Domain to Current Creating a local database requires two steps: (a) ex- List menu command. porting the dataset as a CFXML file and (b) import- Query control display ing the file back into ChemFinder. Once you import the file, save it as a CFX file. It will then be available When you run queries in a domain, they will not be for you to use whenever you need it. displayed as child queries of the domain unless you select Over Current List on the Search menu and Exporting the dataset specify the domain as the active list. To export a dataset: Cancelling the domain 1. Run a query to create the dataset. If you no longer want to use a domain, click the 2. Click the File>Export>CFXML menu command. Search>Domain>Reset to Full Database command The Data Export window opens. again to cancel it. 3. Select the options you want to apply to the Creating an mdb database exported dataset: •In the Data Export dialog box, select a path When working with a large, Oracle-based database and file name for the new database. Use the on a server, it is sometimes convenient to store a File button to browse for a location. subset of the database (dataset) as a local database. • In the lower half of the dialog box, all data ChemFinder local databases are Microsoft Access- fields are selected for inclusion in the based (file extension: MDB), so the exported exported database by default. Clear the dataset must take into account Access naming rules appropriate checkboxes to deselect fields and limitations. you want to omit.

420 • Check the field names to ensure each one names, which are prefixed for subform fields. complies with Access database rules (If necessary, edit the field name by double-clicking Tips for optimizing performance it). When working with a large data base or multiple •On the Text Options tab, select a delimiter and forms, you will want to ensure that you can still other options you want to include: subform work efficiently. To do so, there are a few tech- data, empty records, and headers. You also niques you can use to improve ChemFinder’s per- have an option to save structures in CDX or formance, even when you are working with a lot of CDXML format. data. 4. After you have made your selections, click the Use domain-linked forms Export button. Using a domain offers a significant speed advantage Importing the cfxml file compared to working with the full database. If you Once you have saved the dataset in CFXML for- choose Retrieve All after performing some queries, mat, you must bring it back into ChemFinder to you will get only the domain as the full database. save it as an MDB file. Since the domain is typically much smaller than the NOTE: To avoid conflicts with field name/type definitions, database it was created from, the query and restore close the master database before importing and open a blank commands are executed much faster. form. Another advantage is that the domain is “non-vola- tile”, that is, the view remains on the server until 1. In a blank form, click the File>Import> CFXML you delete it. If you routinely work with a particular menu command and open the file. subset of a large database, creating a domain elimi- The Data Import dialog is displayed. nates the need to perform the initial routine query 2. Select/deselect the fields you want to import and or create a local database. You only need to save the the options you want to apply to the file. domain information by saving the form. The next 3. After you make your selections, click the Import time you open that form, you see only the domain. button. Your dataset is imported into an Access A third advantage is that the sort order at the time database. of creation is preserved. Sorting is a time consum- Exporting to an Excel spreadsheet ing operation. By using a domain, you can sort once and save the preferred order. When you export a BioSAR-derived form with To more information, including how to create a do- multiple subforms into an Excel spreadsheet, you main, see Saving query lists. must take precautions to get all of the subforms correctly exported. This is because the exporter Minimize child tables on a single tab normally uses only the field names, and the BioSAR Whenever a subform appears on screen, Chem- subforms show the same set of fields from different Finder automatically updates the data from the assay tables. On export, they will collide, and the server. If you have a lot of subforms on a single tab, data will not come over correctly. ChemFinder must update all of them at once, po- To prevent this, ChemFinder 11.0 has added a new tentially slowing down your work. So, if you have option on the Text Options tab of the Data Export subforms you need to see only occasionally, put dialog box — Prefix output fieldnames. When this box them on other tabs of the form, so they will not be is checked, the output names will match the input

ChemFinder & BioViz 421 User Guide updated until you activate those tabs. ing and closing a plot window still doesn’t remove it from memory. If you have generated plots you no Remove plots that you are not using longer need, use the View>BioViz Plots>Remove

Administrator Plots that are visible all take at least some process- menu command to delete them, then save the form.

422 Chapter 25: Customizing ChemFinder 11.0

Overview The Preferences dialog box appears with the Display tab on top. You may customize ChemFinder 11.0 in the following ways: • Customize display of your molecules, fonts, pictures and forms. • Customize the Favorites tree • Design the toolbars to your specifications. • Perform automated tasks, such as interfacing with Microsoft Excel, or by using CAL, the ChemFinder 11.0 Automated Scripting Lan- guage. Figure 25.1 Display preferences Setting preferences Structure display The Preferences dialog box allows you to customize To display carbon atoms on methyl groups or on the display of molecules, pictures, and forms, and interior aliphatic or aromatic chains, check the set options for searching and exporting. relevant check boxes in the Carbon labels section. General instructions for using the Preferences dia- To display hydrogen atoms on heteroatoms or on log box: terminal carbons: 1. Click the tab containing the preferences to set. Select the Fill valence option in the Hydrogen 2. Select the preferences, and click the OK button. Labels section. Selecting No implicit means these types are dis- Display preferences played without implicit hydrogens. To set the Display preferences: Click the File>Preferences... menu command.

Figure 25.2 Displaying hydrogen atoms Using keyboard shortcuts When using a form, you can use keyboard shortcuts to show or hide atom-to-atom maps, reaction cen-

ChemFinder & BioViz 423 User Guide ters, atom numbers, and bond numbers. Choosing a small grid spacing allows you to place To use keyboard shortcuts: objects more precisely by snapping to a tighter matrix. Select the Enable keyboard shortcuts check box on Administrator the Display tab of the Preferences dialog box. Color preferences When keyboard shortcuts are enabled, the follow- To set the color preferences: ing keys toggle these properties: Click the Color tab of the Preferences dialog box. • A: show/hide atom numbers • B: show/hide bond numbers • M: show/hide atom-to-atom maps • R: show/hide reaction centers • S: show/hide stereochemistry Scaling structures To scale each structure so that it is as large as possible within its structure box: Click the Fit to box radio button in the Structure Scaling section of the Display tab. To display all structures with a constant bond length: Figure 25.3 Setting color preferences 1. Click the Uniform bond length radio button in the The color tab allows you to specify the color of var- Structure Scaling section of the Display tab. ious interface elements. 2. Select the bond length percentage. To set a color: With Uniform bond length selected, structures may be reduced in size if they are too large to 1. Click the button corresponding to the interface fit within the structure box, but they will never element you want to change. be enlarged. The color dialog box appears. Framing pictures 2. Select the new color. 3. Click the OK button. To select whether the pictures in a form are surrounded by a border: TIP: Some users prefer not to see red highlighting because it masks the atom colors. You can change the highlight color on Select the Framed radio button in the Pictures sec- the Color tab of the Preferences dialog box. Selecting “black” tion of the Display tab. will effectively cancel highlighting, leaving atoms to display in Grid spacing their normal colors. To set the grid spacing (in pixels) on a form: Structural query matching Type in a number, or press the up and down Search Type, Search Details, and Tuning help you arrows to change the current value by one unit in define a query to give the kind of hits you are look- the Grid Spacing section of the Display tab. ing for. The settings are discussed in the chapter on

424 queries under “Search types” on page 348, “Setting ChemFinder 11.0 opening options search details preferences” on page 357, and “Tun- You can set ChemFinder 11.0 to open with the ing” on page 358. ChemFinder 11.0 Opening dialog box or to open General preferences the last form you were using. To set the options for what ChemFinder 11.0 dis- The general preferences let you set: plays when it starts up: • Recent file list size 1. On the General preferences tab: • Startup defaults • Frame styles If you want to...... then • Query save defaults To set the general preferences: start with the opening check the box next to dialog box... Show startup dialog. 1. Click the File>Preferences... menu command. The Preferences dialog box appears. start by opening the check the box next to 2. Click the General tab. last form you used... Reopen last form. The General tab appears.

use a default script... check the box next to Check for external scripts

change which select an entry from window is on top in the Explorer tab: drop- the Explorer window down menu.

select a different select an entry from theme the Frame style: drop- Figure 25.4 Setting general preferences down menu. Structure registration options Table 20 Startup options To have ChemFinder 11.0 present an alert when at- 2. Click the OK button. tempting to enter a structure with an atom in a non-standard valence state: Setting the recent file list size Click the Check valences check box in the Registra- You can set the number of files you opened recently tion section. that ChemFinder 11.0 shows. To have ChemFinder 11.0 confirm when you are To set the list size for the most recent files opened: about to modify data in the database: Type in a number (from 0 to 16), or press the up Click the Ask to commit changes check box in the and down arrows to change the current value by Registration section. one unit in the Recent file list size: option on the General preferences tab.

ChemFinder & BioViz 425 User Guide Changing options with the view menu With atom-to-atom maps shown, equivalent atoms in reactants and products are colored Several structure display options can be set from the same. the View menu, including Atom Numbers, Reac- Administrator tion Centers, Stereochemistry, and Atom Maps in reactions. To display reaction centers:

Select the View>Structure>Reaction Centers menu Figure 25.7 Atom-to-atom maps option. These two preferences affect only the display of reactions. Not checking the boxes means these types are displayed as all other atoms and bonds. Customizing the favorites tree The Favorites Tree is a user-constructed collection of file system objects. It may include folders, sub- folders, ChemFinder 11.0 forms, structure files, and documents of all kinds. Its purpose is to allow you to collect, organize, and access the data and docu- Figure 25.5 Viewing reaction centers ments you use regularly. With reaction centers shown, any bond that changes in the course of a reaction is colored. Additionally, any atoms that participate in reaction centers are circled if none of their adjacent bonds participate in the reaction center.

Figure 25.6 Visualization of reaction centers Figure 25.8 The Favorites tree To display atom-to-atom maps: You can open items in the Favorites Tree from within ChemFinder 11.0 by double-clicking them: Click the View>Structure>Atom-to-Atom Map menu option. if the file is… double-clicking will…

a ChemFinder 11.0 open it. form,

Table 21 Favorites tree options

426 To resort a folder or subfolder alphabetically: if the file is… double-clicking will… Right-click on the folder and click the Sort Folder context menu command. a ChemFinder 11.0 execute it. script, Customizing toolbars

an SD- or RDFile, load it. ChemFinder 11.0 lets you format your toolbars. You can Customize the toolbars by dragging buttons on or off. a ChemFinder 11.0 restore it. query, To open the Customize dialog box: Click the View>Toolbars>Customize menu com- any other type of open it in its source appli- mand. document, cation. The Customize dialog box appears.

Table 21 Favorites tree options There are two ways to add items to the Favorites Tree: • Drag one or more files from Windows Explorer into the Favorites window. • Use the context menu. To create a new folder in the Favorites Tree: 1. Point to the “parent” folder. (The new folder will be a subfolder of this folder.) 2. Right-click and click the New Folder context menu command. 3. Type in a new name for the folder. Figure 25.9 Customizing toolbars To add an item to a folder: To add an option to a toolbar that is already in the ChemFinder 11.0 window: 1. Point to a folder. 2. Right-click and click the New Item... context 1. Click the Commands tab in the Customize dialog menu command. box. A File dialog box opens. 2. Locate the command and drag an option from 3. Browse to the file you want to add, select it, and the Commands window to a toolbar in the Chem- click the Open button. Finder 11.0 window. The item is added to the folder. The option appears where you drop it on a toolbar. To rearrange items or folders in the tree: You can delete a button by dragging it off the tool- Drag the item to a new location. bar.

ChemFinder & BioViz 427 User Guide To return a toolbar to the default settings: plays physical and historical data. 1. Click the Toolbars tab in the Customize dialog box. To display the Periodic Table window: The Toolbars tab appears and shows all of the 1. Click the View>Periodic Table menu option. Administrator toolbars that currently appear in the Chem- Finder 11.0 window.

Figure 25.11 2. Click an element to display its name, mass, and other properties in the top box, and to display its symbol in the bottom edit box. By clicking different elements and numbers sequen- Figure 25.10 tially, you can create a molecular formula in the bot- 2. Click the toolbar you want to return to default tom editable text box. You can then paste this settings, and then click the Reset button. formula into the form for a formula query. The toolbar in the ChemFinder 11.0 window To copy a formula from the Periodic Table to the changes to the default settings. form: To return all the toolbars to the default settings: 1. Drag the text to copy, and then press Ctrl+C. 1. Click the Toolbars tab in the Customize dialog box. 2. Click the OK button in the Periodic Table window to close it. The Toolbars tab appears and shows all of the toolbars that currently appear in the Chem- 3. In the form, click the formula box into which Finder 11.0 window. you want to paste the text and press Ctrl+V. 2. Click the Reset All button. To display data about the selected element in the El- ement Editor, do one of the following: Using the periodic table • Display the desired element and click the dis- ChemFinder 11.0 features a periodic table for data play box at the top of the Periodic Table win- display and formula entry. Selecting an element dis- dow.

428 • Double-click the desired element button. manage ChemFinder data, you will need to customize its behavior using Python scripts. To embed a control:

1. Select the Control box tool on the Forms toolbar. 2. Drag a rectangle on the form. The Insert Control dialog box appears. 3. Select a control from the list. The control appears in the Control box.

Figure 25.12 The Element Editor displays properties of the selected element. The color of the element is shown in the periodic table for that element and in any structure data boxes in which that element is present. Figure 25.13 Adding a spreadsheet to a form To change the color of an element: NOTE: Not all controls listed are suitable for use in 1. Click the Color button in the Element Editor a Control box, but appropriate error messages should 2. Select a color from the Color dialog box and be displayed in such cases. click the OK button 3. Click the OK button in the Element Editor. Customizing controls To reset an element’s color to the default: The behavior of an embedded control can be cus- Click the Revert to Default button in the Element tomized by adding Python scripts to the form to Editor. perform custom actions at given times. The control NOTE: The data of the Periodic Table is stored in a tab- can be accessed via the Automation interface delimited ASCII file called CS ChemFinder 11.0 Custom through the Control property of the corresponding Elements.txt located in your ChemFinder 11.0 system direc- Box object, which is obtained from the Boxes col- tory. It can be easily edited with a text editor or spreadsheet lection of the Document object. program if you want to change default data values. Contact CambridgeSoft support at http://www.cambridgesoft.com/services Embedding ActiveX controls for information on using the Automation interface. You can embed most windowed ActiveX controls on a form. For stand-alone controls, you can embed Scripting, Part I: CAL the control and use it immediately. If the control ChemFinder 11.0 is equipped with its own scripting needs programming, or if you want the control to language, the ChemFinder Automation Language

ChemFinder & BioViz 429 User Guide (CAL). CAL is used to operate the program from The Command drop-down list contains previously the keyboard, or to create custom scripts for auto- entered commands. mating simple operations such as switching be- To rerun a previously entered command:

Administrator tween forms or sending data to Microsoft Excel. 1. Select the command from the list. CAL scripts are stored in text files, with their path- 2. Click the Execute button. names stored in forms. In ChemFinder 11.0, you have the option of storing scripts directly in form For detailed information about the command lan- files. Scripts created in ChemFinder 11.0 are stored guage, see Appendix E, “CAL Commands,” on internally by default. When you open a form which page 469. references external script files, you will be prompted to store the script internally. Getting CAL help If you choose to convert the external script files to To display information about the CAL scripting internal, the scripts will be saved when the form is language: saved, and the original script files may be deleted. Click the Help button in the Enter CAL Com- Scripts originally saved as internal may be also be mand dialog box. saved externally. The CAL Scripting Help window appears con- TIP: You can save the form with a different name, and the taining commands, variables, and syntax notes. original will remain untouched (in which case deleting the script files would not be a good idea). If you choose to leave the form unmodified, the alert will continue to show up every time the form is opened. To suppress the prompt: 1. Click the File>Preferences... menu command. 2. Click the General tab. 3. Deselect the Check for external scripts checkbox, then click the OK button. Figure 25.14 CAL help window To execute CAL commands: TIP: In ChemFinder 11.0 this window is resizable. 1. Click the Scripts>Command Line menu command. Creating a script The Enter CAL Command dialog box appears. 2. Type in a single CAL command. To create a script: Click the Help button to see CAL Scripting 1. Create a button on a form. Help. 2. Label the button. 3. Click the Execute button to run the command. 3. Right-click and click the Edit Script context menu You can keep entering commands, one by one. command. 4. When you have finished running commands, click the Done button.

430 The CAL editor appears. Debugging a script You can step through a script line-by-line when debugging it. To view a script line-by-line: 1. Click the Scripts>Command Line menu command. The Enter CAL Command dialog box appears. 2. Type “step on” and click Execute. This turns on the step mode, where each step is displayed. 3. Run a CAL script by doing one of the following: Figure 25.15 The ChemFinder 11.0 script editor Import 4. Type in your script commands, or use the If your script Then button to import an existing script. 5. Click the OK button to create a new file. appears in the Scripts choose the appropriate TIP: You can still create scripts in Notepad or another text menu. script. editor if you wish. Save the file with extension .cfs in the …\ChemFinder 11.0\System subdirectory if you want the does not appear in type call and the name name of the script to appear on the Scripts menu. the Scripts menu. of your script in the The CAL editor is a simple, resizable text-entry Enter Script window. It accepts carriage returns and tabs. To Command dialog box, copy /paste, use Ctrl+C/Ctrl+V. To undo or redo then click Execute. (last change only) use Ctrl+Z. Table 22 The Verify button runs the script through the CAL command parser. The parser checks only that lines 4. Press any key except Escape to execute the com- begin with recognized keywords, so just because a mand and go to the next command. script is parsed without error does not mean it will As each step is encountered, it is displayed in run correctly. the status line. The Properties button displays a dialog box used to 5. Press the Esc key to stop debugging the script. specify whether the script is to be stored in an ex- 6. Type step off in the Enter Script Command dialog ternal file or internally, and to provide a file path or box, to exit the debugging mode. script name. You can assign a script any name you like, but the name must be unique among scripts on Trigger scripts the current form. Trigger scripts run in response to certain pre- The OK button saves the script. The Run button defined events. A trigger script can, for example, saves the script and runs it. automatically load a box with data calculated from To execute a script not assigned to a button: the contents of another box whenever you move to a new record. Choose the script from the Scripts menu. NOTE: To execute a script that does not appear on the You access a trigger script from the Run script on list- menu, use the Command line and enter “Call