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.
Q. Do you have a script to decompose solvent accessible surface area (SASA) contributions from various parts of a protein? Furthermore, can I get the difference in these terms upon ligand binding?
A. Yes, we have a new script called binding_sasa.py that calculates the total change in solvent accessible surface area (SASA) upon ligand binding. It also provides a decomposition of various contributions from different residue types. The descriptors from these calculations can help elucidate binding site behavior or be used in predictive models such as those in recent work by Nuñez et al. (J. Chem. Inf. Model., 2010, 50(4), 480-486). This script is run from the command line, although a graphical interface may be developed if there is sufficient user demand.
Q. I just performed a conformational search and generated more conformers than I had expected. How can I cluster the results and obtain a representative subset of conformations?
A. The script conformer_cluster.py performs hierarchical clustering based on positional or torsional RMSD, and can cluster using all atoms in the molecule or just a user-specified subset. Clustering statistics, dendrograms, and distance matrices can all be visualized. There are various options for loading cluster results into a Maestro project, such as creating an entry group in the Project Table for each cluster or retaining only a single representative conformation from each cluster. This script can be run from either a graphical interface or the command line.
Q. I would like to create 2D diagrams of a protein-ligand complex, similar to LigPlot. Do you have a tool to do this?
A. We recently posted a preliminary version of our Ligand Interaction Diagrams, which generates a simplified 2D representation of a 3D protein-ligand complex (see Figures below). The 2D ligand structure is optimized to match the 3D structure as closely as possible, which helps ensure that binding site residues are accurately positioned in the 2D diagram – in fact, the 2D view can be synced with Maestro’s 3D workspace.
The 2D diagrams have several unique features that convey information about the binding site. For example, the font size used for a residue name corresponds to the depth of that residue in the 3D view, and residue markers are colored according to residue type (green=hydrophobic, cyan=polar, red=negative, purple=positive). H-bonds to side chains are represented as dashed lines, whereas H-bonds to backbones are represented as solid lines. Per-atom solvent accessible surface area is denoted by yellow markers on the ligand structure, and the marker size represents the amount of exposure.
Users can set many display options, such as atom color, residue color, background color, transparency, image format and resolution, and more. While the current version is quite useful, we’re still adding features for the official release of Ligand Interaction Diagrams in Schrödinger Suite 2011. In the meantime, experiment with the current version and let us know what you think. This script can be run from within Maestro or in a standalone mode from the command line.
Figure 1: Above, some examples of ligand-binding sites shown in a simplified 2D representation using the Ligand Interaction Diagram script. Font size corresponds to residue depth in 3D space and residues are colored according to residue type.