Dr. Sherman works closely with researchers using Schrödinger software for molecular modeling and drug design projects. All of the scripts discussed here can be downloaded free of charge from the Schrödinger Script Center, or by using 'Update...' from the Scripts menu in Maestro.
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Q. In the last newsletter you mentioned a script to create 2D diagrams of a protein-ligand complex, similar to LigPlot. I tried using it, but got a license error. What license do I need to run this program?
A. We have removed the license restrictions on our Ligand Interaction Diagram (LID) script, and it can now be run with just a standard Maestro license. If you’re already using Maestro, you should now be able to use the Ligand Interaction Diagram. The initial version of the LID script received a lot of positive feedback and as a result it will be part of the standard Maestro release in Suite 2011. (See the next question for a list of new LID features in the next release.)
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Q. I was able to create a nice-looking 2D image using the Ligand Interaction Diagram script, but it contains more information than I’m used to seeing in a 2D schematic of a binding site. What do the color codes and other features mean, and why is the 2D structure oriented differently than expected?
A. The Ligand Interaction Diagram script is designed to generate simplified 2D binding site representations while maintaining accuracy in the placement of residues. We achieve this by generating the optimal 2D ligand image based on the 3D conformation. Hence, depending on its 3D conformation, the 2D ligand might not be drawn exactly the same as it might look in your lab notebook – but this allows the script to better place residue markers. In Suite 2011 Ligand Interaction Diagrams will always display a consistent 2D representation for congeneric molecules.
Font size is used to represent the depth of a residue in the 3D view – residues “closer” to the viewer are shown in large font, and residues that are “far away” are shown in a small font. H-bonds to side chains are represented as dashed lines, whereas H-bonds to backbones are represented as solid lines.
Residue markers are colored according to residue type (green=hydrophobic, cyan=polar, red=negative, purple=positive). Yellow markers on the ligand structure denote per-atom solvent accessible surface area, and the marker size represents the amount of exposure.
In Suite 2011, Ligand Interaction Diagrams will also display pi-cation interactions, cofactors, and a legend.
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Q. I would like to do a quick, interactive minimization of selected atoms in the Maestro Workspace without going through one of the more complicated interfaces, like MacroModel or Impact. What is the best way to do this?
A. The absolute easiest way to do an interactive minimization in Maestro is to press Ctrl+M. This will minimize all atoms in the Workspace (or just the selected atoms, if there are any) with the OPLS 2005 force field.
However, we have a script called interactive_minimizer_gui.py that allows you to do this with a few more options. For example, you can choose to use only the repulsive part of the vdW potential or to ignore electrostatics, which can be useful for certain applications.
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Q. I would like to display the hydrophobic interactions between a ligand and protein. I tried to do this by only showing the good contacts using Maestro’s Measurements panel (under Tools > Measurements > Contacts in the Maestro menu), but it required me to exclude polar atoms using an Atom Selection Language (ASL) expression. Is there an easier way to do this?
A. Yes, we have a script called display_hydrophobic_interactions.py for this task. The ligand and the protein are automatically detected and the polar atoms will be excluded from the display of good interactions.
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Q. I previously used a script called align_binding_sites.py. The script gave very nice alignments of binding sites, but I can no longer find it on the Script Center. Is it still available?
A. Yes, it is. This was one of our more popular scripts on the Script Center and as a result it’s now a built-in part of Maestro. Just choose Align Binding Sites under the Tools menu in Maestro.
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Q. I have 2 conformations of the same protein and would like to color the atoms by the Euclidean distance between the 2 structures. Is this possible?
A. This is a good way to quickly identify or illustrate protein conformational changes, and can easily be done using the script colordeviation.py. For 2 selected entries in the Project Table, the script will compute the distance between pairs of atoms and color them by deviation using the spectrum below:
violet 0.0 A to 0.1 Å
blue 0.1 A to 0.5 Å
green 0.5 A to 1.0 Å
yellow 1.0 A to 2.0 Å
orange 2.0 A to 3.0 Å
red greater than 3.0 Å
The script expects that the structures are in the same frame of reference (for example, by using Align Binding Sites, as described above) and that the numbering scheme is consistent between the 2 structures.
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