CHEMICAL REPRESENTATION BIOVIA DATABASES 9.5 Copyright Notice ©2015 Dassault Systèmes. All rights reserved. 3DEXPERIENCE, the Compass icon and the 3DS logo, CATIA, SOLIDWORKS, ENOVIA, DELMIA, SIMULIA, GEOVIA, EXALEAD, 3D VIA, BIOVIA and NETVIBES are commercial trademarks or registered trademarks of Dassault Systèmes or its subsidiaries in the U.S. and/or other countries. All other trademarks are owned by their respective owners. Use of any Dassault Systèmes or its subsidiaries trademarks is subject to their express written approval. Acknowledgments and References To print photographs or files of computational results (figures and/or data) obtained using BIOVIA software, acknowledge the source in an appropriate format. BIOVIA may grant permission to republish or reprint its copyrighted materials. Requests should be submitted to BIOVIA Support, either through electronic mail to [email protected], or in writing to: BIOVIA Support 5005 Wateridge Vista Drive, San Diego, CA 92121 USA No-Structures 28 Contents Chapter 2: Reaction Representation 29 Introduction 29 Overview 1 Reaction Mapping 29 Audience for this Guide 1 Mapping Reactions Automatically 30 Prerequisite knowledge 1 Mapping Reactions Manually 31 Related BIOVIA Documentation 1 Stereoconfiguration Atom Properties in Chapter 1: Molecule Representation 3 Mapped Reactions 32 Substances, structures and fragments 3 Properties of Bonds in Mapped Reactions 32 The BIOVIA Periodic Table 3 Simple Bond Properties 32 Atom Properties 3 Combined Bond Properties 33 Charges, Radicals and Isotopes 3 Example: Ambiguity in the fate of reacting Valences and Implicit Hydrogens 4 atoms and bonds 33 Example: Multiple fates of bonds in Default Valences 4 products 34 Explicit Valence 5 Stereogroup Information in Reactants and Rules for Calculation of Valence and Implicit Products 34 Hydrogen 5 Chapter 3: Markush (Rgroup) Structures 36 Bond Types 5 Library Representation 36 Aromaticity 7 The Root Structure 37 Tautomers 8 Rgroups and Rgroup Members 38 Salts 8 Nested Rgroups 38 Tetrahedral Stereochemistry 9 One Attachment Point 40 Grouping Related Stereogenic Centers 9 Two Attachment Points 40 Structures with One Stereogenic Center 10 Unconnected Rgroup Atom 41 Structures with more than one Stereogenic Center 11 Null Members 42 Markush Structures Differ From Markush Chiral Labels 13 Queries 43 Rules for Unambiguous Representation of Tetrahedral Stereochemistry 15 Enumeration of Markush Structures 43 Original BIOVIA Representation of Scaffold-based Enumeration 43 Tetrahedral Stereochemistry 16 Reaction-based Enumeration 44 Examples of Stereogroups 16 Rgroup Decomposition 44 Example 1: Racemic Mixture 16 Chapter 4: Homology Groups 47 Example 2: Acquiring Increasing Amounts of About Homology Groups 47 Information on the Stereochemistry of a Creating Substructure Search (SSS) Queries 47 Sample 17 Limitations 48 Example 3: A Mixture of Epimers in a Reaction Product 20 Chapter 5: Attached Data 49 Stereochemistry of Allenes and Biaryls 23 Introduction 49 Cis and Trans Stereochemistry 24 Sgroup Fields 49 Meso Compounds 24 Required Sgroup Fields 49 Spiro Compounds 25 Sgroup fields for condensed representation of biopolymers 49 Chemical and Data Substance Groups (Sgroups) 25 Sgroup field for stereochemical purity at stereogenic centers 50 Data Sgroups 26 Sgroup fields for polymer representation 50 Abbreviated Structures 26 Reserved Names for Sgroup Fields 51 Multiple Groups 26 Guidelines for Defining Your Own Attached Other Chemical Sgroups 27 Data 51 Structural Uncertainty 27 Examples of Attached Data 51 Star Atoms (*) 27 Distinguishing Relative Stereoisomers 51 Abbreviation attachment atom (SAP) 69 Isotopic Purity 53 Creating and Enforcing Conventions for Creating Sgroup Fields in Your Database 53 Biopolymer Representation 70 Data Sgroup Queries 54 Choose One Convention for Each Chemical Entity 70 Related Documentation for BIOVIA Draw 55 Use Standard Abbreviations 70 Chapter 6: Biopoloymer Representation 56 Related Documentation for BIOVIA Draw 71 Configuring Databases for Biopolymer Registration and Searching 56 Subsequence Searching in Isentris Applications 71 Condensed Representation of Biopolymers 56 Subsequence Search Differs from Substructure Search 71 Hybrid representation (template representation of residues) 56 BIOVIA Draw Programming Interface (API) for subsequence search 72 *Atoms Alone 57 Implementing subsequence search for full Pseudoatoms Alone 57 structure representations 72 *Atoms and Pseudoatoms 58 Chapter 7: Mixture Representation 73 Summary of Biopolymer Structure Ordered and Unordered Mixtures 73 Conventions 58 Using * atoms for Unspecified Structures in Compatibility of Sequences Created in Mixtures 73 ISIS/Draw 59 Examples of Mixtures 74 ISIS/Draw sequences use the full structure convention 59 Unordered Mixtures 74 ISIS/Draw residue templates lack explicit Reaction product 74 attachment atoms 59 Mixture of stereoisomers 74 Stereochemistry of ISIS/Draw residue Aspirin tablet 75 template 60 Ordered Mixture 76 Compatibility of Condensed and Full Chapter 8: Polymer Representation 77 Structure Conventions 60 Introduction to Polymer Representation 77 Required Sgroup Fields for Biopolymer Representation 60 Structure-based and Source-based Representation 77 Sgroup field for identifying attachment atoms 60 Polymer Bracket Types 78 Sgroup field for *atom representation 61 Structural repeating unit (SRU) brackets 78 Structures Used in Biopolymer Representation 62 Monomer brackets (mon) 78 Biopolymer Residues 62 Mer brackets (mer) 78 Single-attachment Groups 62 Copolymer brackets (co) 78 Protecting groups 62 Additional polymer brackets 79 PEG molecules 62 Cyclization and Phase Shifting 80 Special Features of Abbreviated Structures 63 Polymer Repeat Pattern 80 Template Format for Biopolymer Residues 63 Polymers with two crossing bonds 80 Abbreviation Class 63 Ladder-type Polymers 81 Terminal Leaving Groups 64 Polymers with three or more brackets 83 Order and Bond Matching Attributes of Polymer End Groups 84 Attachment Atoms 65 Why Are Representation Conventions Attachment atoms on reactive chains 66 Important? 84 Explicit hydrogen leaving groups on Guidelines for Graphical Representation of attachment atoms of reactive chains 66 Polymers 85 Explicit hydrogen leaving groups on Structure-based and source-based histidine 68 representation 85 Molfile Features in Biopolymer Templates 69 Stereoregularity in Polymers 86 Abbreviation class (SCL) 69 Using Attached Data in Polymer Representation 86 Sgroup subscript (SMT) 69 Required Attached Data for Polymer Stereochemistry (STE) 108 Representation 86 Tautomer bonds (TAU) 109 Polymer or copolymer type 86 Salts and Parent Compounds (CHA, ION, Stereoregularity 86 FRA, SAL) 109 Guidelines for Defining Additional Attached Charge (CHA and ION) 109 Data 87 Fragments (FRA) 109 Examples of Structure-Based Representation 88 Hydrogen count (HYD) 110 Regular Homopolymers 88 Salts (SAL) 110 Simple homopolymers 88 Alternative Structure Representations (MET, Stereoregularity 89 RAD, VAL, IgnoreChargesInPiSystems) 110 Ladder-type polymers 89 Metal bonds (MET) 110 Irregular Homopolymers 89 Radicals (RAD) 110 Alternating and Periodic Polymers 90 Valence (VAL) 111 Statistical, Random, and Unspecified Substance Groups (Sgroups) 111 Copolymers 91 Attached Data (DAT) 111 Unspecified Copolymers 91 Polymer end groups (end) 111 Random copolymers 92 Mixtures (MIX) 111 Statistical copolymers 93 Monomer/SRU uniqueness (MSU) 111 Regular Block Copolymers 93 Polymers (POL) 112 Ordered diblock 93 Polymer Type (TYP) 113 Block copolymer with junction unit 94 Dependencies Between Switches 113 Segmented block copolymers 94 Examples of the Interactivity of Flexmatch Star block copolymers 96 Switches 113 Irregular Block Copolymers 96 Sulfones 113 Chemically Modified Polymers 97 Sulfoxides 114 Graft Polymers and Copolymers 98 Thiocarboxylic acid salts 114 Single graft at a known site 99 Organometallic Complexes 114 Mixed graft at a known site 99 Flexmatch Search of Structures with Cross-linked polymers 99 Tetrahedral Stereochemistry 116 Examples of Source-based Representation 101 Absolute Configuration 118 Guidelines for Source-based Representation 101 Relative Stereoconfigurations (OR groups) 119 Homopolymers 102 Example 1 119 Alternating and other Periodic Polymers 102 Example 2 119 Copolymers from Monomers that do not Example 3 120 Homopolymerize 103 Example 4 122 Statistical, Random, and Unspecified Example 5 122 Copolymers 103 Example 6 124 Unspecified copolymers 103 Mixtures of Relative Stereoconfigurations Random Copolymers 104 (AND groups) 124 Statistical Copolymers 105 Flexmatch Search of Polymers 126 Block Copolymer 105 Useful Combinations of Flexmatch Switches 128 Chapter 9: Exact Search (Flexmatch) 107 Exact Match/As Drawn 128 Flexmatch Switches 107 Exact Match/As Drawn plus Tautomers 129 How to Specify Switches 107 Tetrahedral Stereochemistry 129 Description of Switches 108 Cis/Trans Geometric stereochemistry 129 Isotopes (MAS) 108 Exact Match/As Drawn plus Stereoisomers 130 Bonds (BON, STE, TAU) 108 Tetrahedral Stereochemistry 130 Bond (BON) 108 Cis and Trans Stereochemistry 131 Original Tautomer Search 131 group Exact Match/As Drawn plus Salts 131 Allowing Multiple Bond Types 147 The Least Restrictive Flexmatch Switches 133 Bond query feature: Any bond 147 Exact Match/As Drawn Polymer Search 133 Hydrogen query is a special case 147 Sourced-based and Structure-based Bond query feature: Aromatic bond 147 Polymer Search 133 Bond query feature: Single/double bond 148 Copolymer