Dr. Sherman works closely with researchers using Schrödinger software for molecular modeling and drug design projects. In this newsletter, Dr. Sherman talks about early access to Schrödinger’s new shape-based screening tool, how to filter Glide poses based on the degree of extension, and more. All of the scripts discussed here can be downloaded from the Schrödinger Script Center.
Q: I heard there is a new shape-based screening tool from Schrödinger. How can I access it?
A: Yes, we do have a new shape-based tool which is now available in our most recent update of Suite 2007.
This tool is a fast way to perform flexible superposition and
shape-based virtual screening. The methodology was recently described
in an online seminar by the developer, Dr. Steve Dixon. This tool can operate on an input file (SD or Maestro) or can search a Phase database; and can be run from either the command line ($SCHRODINGER/phase_shape) or from a graphical interface (phase_shape_gui.py – available on the Script Center). In the Suite 2008 release this functionality will be available from within the Phase menu of Maestro.
Q: I would like to filter my Glide poses or conformational search results based on the extendedness of each conformation. Is there a script to do this?
A: We just put our Compute Extendedness of Conformations script (conformer_geom_extent.py) on the Script Center.
This script computes the degree of extension for a set of conformers
based on the work of Perola and Charifson as published in
"Conformational Analysis of Drug-Like Molecules Bound to Proteins: An
Extensive Study of Ligand Reorganization upon Binding," J. Med. Chem., 2004, 47, 2499-2510.
Q: In addition to the Glide scoring terms I would like to get the energetic contribution from each residue in the binding site. What is the easiest way to do this?
A: Actually, there are now two scripts that can do this. As was discussed in the Fall 2007 newsletter, the Compute Component Interactions script (component_interactions.py) uses MacroModel to post-process docking results in order to compute interactions either between the ligand and each of a set of receptor residues, or between functional groups of the ligand and the receptor. In addition, we now have a script to compute the receptor residue contributions from directly within Glide during a calculation. A script to do this is on the Script Center called glide_residue_interactions.py. The following interactions are written to the Glide log file for each residue selected: Coulomb, vdW, H-bond, and closest atom distance. The script interface can also be used to create a csv file from the log file data. Plans are underway to integrate much of this functionality into Glide for Suite 2008.