Teaching with SCIGRESS Exercises on Molecular Modeling in Chemistry Crispin Wong and James Currie, eds. Pacific University Teaching with SCIGRES Molecular Modeling in Chemistry Crispin Wong and James Currie Editors Pacific University Forest Grove, Oregon 2 Copyright statement © 2001 - 2012 Fujitsu Limited. All rights reserved. This document may not be used, sold, transferred, copied or reproduced, in any manner or form, or in any medium, to any person other than with the prior written consent of Fujitsu Limited. Published by Fujitsu Limited. All possible care has been taken in the preparation of this publication. Fujitsu Limited does not accept liability for any inaccuracies that may be found. Fujitsu Limited reserves the right to make changes without notice both to this publication and to the product it describes. 3 Table of Contents Exercises 7 Part 1: General Chemistry Experiment 1 Calculating the Geometry of Molecules and Ions 16 Experiment 2 Kinetics of Substitution Reactions 29 Experiment 3 Sunscreen and Ultraviolet Absorption 38 Part 2: Organic Chemistry Experiment 4 Evaluations of Conformations of Menthone and Isomenthone 46 Experiment 5 The Evelyn Effect 52 Part 3: Physical Chemistry Experiment 6 Investigating the Resonance Stabilization of Benzene 63 Experiment 7 Investigation of the Rotational Barrier in N-N-dimethylacetamide 68 Part 4: Inorganic Chemistry Experiment 8 Polarities of Small Molecules 75 Experiment 9 Structures of Molecules Which Exceed the Octet Rule. 77 Experiment 10 Comparison of Gas Phase Acidities of Binary Hydrogen Compounds 81 Experiment11 Crystal Lattices and Close Packing Sites 84 Experiment 12 Identification and Execution of Symmetry Operations 91 Experiment 13 The Relationship Between Infrared Spectra and Molecular Geometry 96 4 Experiment 14 Molecular Orbitals of Simple Molecules 103 Experiment 15 Molecular Orbitals of Octahedral Transition Metal Complexes 108 Experiment 16 Relative Ligand Field Strengths 113 Experiment 17 Stereoselectivity of Chiral Chelating Ligands in Metal Complexes 118 Part 5 Working with Biomolecules and docking 123 Importing and Cleaning Protein Crystal Structures 124 Viewing and Analyzing Proteins, Ligands, and their Complexes 133 Discovering Active Sites of Homologous Proteins by Sequence Alignment 144 Automated Docking and Scoring 154 Discovering Inhibitors by Automatically Scoring and Docking Libraries using PMF and quantum docking 160 Part 6 Basic QSAR analysis in SCIGRESS 164 Appendix I Understanding FastDock genetic algorithm settings 169 5 6 I. Building Basics Build: 1. Choose Start | Programs | SCIGRESS Suite | SCIGRESS. The application opens, containing an empty document window referred to as the workspace. 2. Click on the Drawing pencil tool icon. Your cursor turns into the Drawing pencil cursor shown to the right. 3. Select the arrow button in the Element Type box located on the left of the Style bar. A drop down list of elements appears. Select C-Carbon. The default hybridization is sp3. 4. Look in the Hybridization box. If the hybridization is not sp3, click on the arrow. From the drop down menu, select sp3-tetrahedron. The carbon atom TIP is now sp3 hybridized. For most actions, you can click on Edit | Undo to 5. Click once in the workspace to deposit a single carbon (C) atom. Do not undo your last command. double click unless you want multiple atoms. 6. Click on the existing C atom, hold the button down and drag away (click-drag). Release the mouse button. Another C atom appears connected to the first C atom with a with a single bond. Add three more C atoms by doing a click-drag. You should have a string of five C atoms. 7. Return to the Element Type list and select O-oxygen. Make the atom sp3 hybridized. 8. Click-drag from the C next to the end. A red O atom is connected to the C atom. 9. Click on the Select tool icon. The cursor changes into an arrow shown to the right. 10. Click in the workspace but not on any atoms or bonds. This selects all atoms and bonds in a molecule. 11. Select Action | Beautify | Comprehensive (ctrl + b). If the skeleton structure was built correctly, the correct number of hydrogen atoms is present and the 3 angles are proper for sp hybridization. 7 12. Click File | Save as… . Save the molecule with the name “2-pentanol” in the appropriate location. The molecule saves as a chemical sample “.csf” file type. II. Viewing the Structure Open the molecule “2-pentanol” from Exercise I in the Editor. Translate, Rotate, and Zoom 1. Change the position of the molecule by translating, rotating, and zooming. Experiment with each of these three modes. Rotate: Click on the Rotate icon. In the window there is a circle around the molecule and your cursor is an arrow. Click and drag your cursor to rotate the molecule. Movement inside the circle produces rotation around the X and Y axes while movement outside the circle allows rotation around the Z axis. Translate: Click on the Translate icon. The cursor appears as a hand. Click and drag the mouse to move the molecule around on the screen. Zoom: Click on the Zoom icon. The cursor becomes a magnifying glass. Click and drag the magnifying glass up or down to zoom in or out. The following key combination is very useful for repositioning the atom: Press the Ctrl + f to center the structure and scale the molecule to fit the window. If only one atom is selected, the structure is centered around the selected atom but no scaling is done. Press i to return the molecule to the initial scale and orientation. 2. Enter the Select tool mode. 8 3. Select View | Styles | Atoms... The Atom Attributes dialog box opens. The options in the Atom Attributes box allow you to change the way the atoms and bonds are displayed. 4. Click on the Label tab to display the list of label options. NOTE Viewing with labels 5. Click in the square next to Atomic Symbol. The square has a check mark inside, enables easy inspection indicating that the option is selected. Click OK. The element letter appears on of charges. However, the each atom. structures are more suitable for formal 6. reports without the Select View | Styles | Atoms... Click on the Shape tab to display the list of labels. options. Locate the “Scale Spheres such that” section. The default view is usually scaled to 0.2 times the van der Waals radius. To view the atoms at their true size, set this number to be 1.0. This mode is known as the space-filling view. A quick way to reach the space-filling mode is to click on the space-filling icon on the toolbar. The icon is a short cut for the command View | Atoms & Bonds | Space Filling. Experiment with the different view options. 7. Return the molecule to “0.2” atom scaling before continuing with other exercises. 9 III. Modifying structures Open the “2-pentanol” file from Exercise I, and change the structure to: 1. Click on the C-O bond using the Select tool to select the bond. Click on the arrow in the Bond type box on the Style bar. A pop up menu appears. Select Double; the C-O bond is now double. The sp3 hybridization is wrong for atoms with double bonds. 2. Click on the C atom connected to the O atom. Select sp2 - trigonal plane in the Hybridization box. 3. Repeat this process for the O atom and set it also for sp2 hybridization. 4. Select Action | Beautify | Comprehensive. 5. Save 2-pentanone structure. You will use it later in the tutorial. IV. Further modifications In this section we will use several methods to add or change atoms. These methods are generally interchangeable. Start with “2-pentanol” from Part III and modify it in the following manner: 1. Click on the Select tool icon to enter the Select tool mode. NOTE 2. Select the hydrogen (H) atom that you want to replace with a bromine (Br) In this case Beautify atom. would have corrected the hybridization but this 3. Click on the arrow in the Element type box on the Style bar. In the pop up menu, exercise was intended to select Periodic Table. A Periodic Table opens in a dialog box. show how to change the hybridization. 4. Select the element Br. Click OK. The H atom is replaced with a Br atom. Look in 3 the Hybridization box; make sure the hybridization is sp . 5. Check the Charge box; make sure the charge is 0. If the charge is not 0, you can change the charge by clicking the up arrow to get a positive charge and the down arrow to get a negative charge. 6. Select the O atom. In the Charge box, change the charge to +1. 7. Select Action | Beautify | Comprehensive. The missing hydrogen is added and the bond distances and angles are corrected. 10 8. Select in order, the H atom connected to the O atom, followed by the O atom and then the C atom attached to the O. 9. Select Action | Geometry Labels | Bond Angle. A Bond Angle dialog box opens, displaying the bond angle in degrees. You can label, record or adjust the angle. In this case, you will label the angle. Select Define Geometry Label, and then Unlock Geometry. Unlock geometry allows the angle to change as you modify the structure. Click OK. The label appears on the bond angle. In the same manner, you can label the atom distance by selecting two bonded atoms and select Action | Geometry Labels | Atom Distance. 10. Select File | Save as. The Save as command leaves the last saved version of the file intact, and saves the current molecule as a different file.