Dr. Sherman works closely with researchers using Schrödinger software for molecular modeling and drug design projects. In this newsletter, Dr. Sherman talks about covalent docking, quickly generating molecular surfaces, and more. All of the scripts discussed here may be downloaded from the Schrödinger Script Center , or using ‘Update...' from the Scripts menu in Maestro .
Q: I have a set of structurally similar proteins that have different residue numbering. How can I renumber them to be consistent with each other based on their alignment?
A: We have a script to renumber proteins by 3D alignment (AdjustResidueNumbering.py) that can be found under the Workspace Tools category of the Scripts menu, and may be run from within Maestro.
It will perform a 3D structural superposition of the proteins and then
renumber the residues based on the numbering of the template. In
addition to being useful for general viewing and analysis, the
renumbered proteins can be used to quickly get everything aligned
properly (via the ‘Align by Residue Number’ option accessed by
right-clicking in the title section of the Sequence Viewer).
Q: I find it helpful to view surfaces for protein-ligand complexes. While the Molecular Surfaces panel under the Display menu has a lot of nice options, I am interested in an interface where I can simply select a ligand and generate a surface for both the ligand and the protein?
A: There is a script called simple_surface.py
under the Interfaces and Automation category of the Scripts menu that
is designed to do exactly this. It can generate surfaces for the ligand
and receptor separately, or for the whole complex. It is very fast and
easy to use.
Q: I have a new project that involves covalent inhibitors. I used Glide docking with positional constraints and that worked well to get good poses, but I am interested in trying to sample the ligand with the actual covalent bond. Is that possible?
A: Yes, we have a new script called Prime Covalent Docking (covalent_docking.py) that can be found in the Docking category of the Scripts menu. Using Prime, it treats ligands with the same loop sampling methodology as used for terminal tails. The attachment residue can also be sampled, if desired. Multiple ligands can be docked sequentially, even if they have different reactive groups, by specifying the SMARTS pattern for each attachment point.