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 choosing Update from the Scripts menu in Maestro.
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Q. I have two files of ligands and want to find the ligands that are common to both files. How can I do that?
A. Compare Ligand Files (compare_ligand_files_gui.py) can do exactly that. It can also return the ligands that only appear in one file and not the other.
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Q. I have a lot of protein-ligand complexes and want to perform cross docking between all ligands and receptors. Is there an automated way to do this?
A. Glide Cross Docking (xglide_gui.py) automates the cross docking process. There are many options, such as automatic preparation of the ligands and receptor. Also, additional ligands can be added from a file. In addition, there is an option to use SiteMap to detect binding sites and dock to each of the top sites. The results are analyzed and tabulated with energies and RMSD values. New in Suite 2012, we have added a graphical interface to Glide Cross Docking, so the script can be run from Maestro or the command line.
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Q. I have read a few papers recently about structure-based energy pharmacophores and would like to apply this protocol to my project. How can I do this?
A. Those papers were likely using the methodology that we developed in 2009 and 2010 (Loving et al. J. Comp. Aided Mol. Des. 2009, 23 (8), 541-554 and Salam et al. J. Chem. Inf. Model. 2010, 49 (10), 2356-2368). The method, called e-Pharmacophores (epharmacophores_gui.py), uses energetic descriptors of protein-ligand interactions derived from Glide XP calculations to determine which pharmacophoric features of the ligand contribute most to binding. The most energetically important features are used to generate a pharmacophore that can be used for virtual screening. The method can also be applied to docked fragment molecules to create an e-Pharmacophore based on the best features from any fragment.
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Q. I heard a presentation about a method called BREED that combines docked or crystallized molecules to make novel compounds with components from each molecule. Do you have a way to do this?
A. Yes, this method was developed at Vertex Pharmaceuticals and published by Pierce et al. J. Med. Chem., 2004, 47 (11), 2768-2775. The method finds overlapping bonds from different molecules and swaps the two sides of the molecules to create new hybrid molecules. Multiple iterations can be performed to create molecules that contain pieces from more than two molecules. Schrödinger has licensed this method from Vertex and it is available from our Script Center (breed.py). Note that input ligands need to be in the same frame of reference (either docked to the same receptor or from multiple superimposed crystal structures).
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Q. Do you have a way to compute the principal moments of inertia for a molecule?
A. Yes, this simple calculation can be performed using Compute Principal Moments of Inertia (calculate_pmi.py). This script will run on all entries in the Project Table and a new property will be created for each of the three principal moments.