Dr. Sherman works closely with researchers using Schrödinger software for molecular modeling and drug design projects. In this newsletter, Dr. Sherman talks about automating grid formation and docking, a simplified interface for medicinal chemistry tasks, and more. All of the scripts discussed here can be downloaded from the Schrödinger Script Center.
Q: I would like to perform cross docking calculations on a large number of proteins/ligand complexes. Is there a way to automate the process of generating the grids followed by docking all of the ligands to each of the grids?
A: xglide.py
can do exactly this, and more. The script is run from the command line
and takes a simple input file that specifies all of the structures to
be used and the docking options. It is preferable if your structures
are prepared within Maestro so you can analyze them, but xglide.py has options for performing most of the steps available in the Protein Preparation Wizard.
The script also allows for automatic scaling of the receptor vdW in
steps to determine an optimal scaling for a given receptor.
Q: I am looking for a simple interface to perform some common medicinal chemistry tasks. I appreciate that many people want all of the options in your interfaces, but do you have something that just exposes the most important features of each task?
A: We do have a simplified interface for medicinal chemistry tasks (medchem.py).
In this simple gui there are tabs to perform a minimization, torsional
scan, and conformational search, and to generate QM charges for a small
molecule. Each task has a few options, like the solvent or atoms to
use. In addition to the output structures, plots are generated for the
torsional scan and conformational search so that the energy at each
point is interactively coupled with a structure in the Workspace.
Q: Along the same lines of the previous questions, I would like to simply dock a set of ligands to my protein in one step (i.e. combine grid generation and docking). Can I do that?
A: We have a script to do exactly that – one_step_glide.py. It does not have all of the options accessible from within Glide
(i.e. it has H-bond constraints but not positional or core constraints)
but it is very easy to use and will automate the process of grid
generation and docking.
Q: Is there a way to generate separate complexes for each pose within a Glide poseviewer file?
A: The script pv_convert.py can generate a set of complexes from a poseviewer file by combining the receptor structure with each one of the subsequent poses. It can also take an input complex and break it into a poseviewer file, which can then easily be used in other applications like Prime MM-GBSA.