Predicting Protein Ligand Binding Sites by Combining Evolutionary Sequence Conservation and 3D Structure
Figure 7
Examples of difficult structures.
For each structure, evolutionary sequence conservation has been mapped to the surface of the protein backbone (all atoms in pane (C)) with warmer colors indicating greater conservation. Bound ligands are shown in yellow, and the pocket predictions of ConCavity are represented by green meshes. (A) The ActR protein (PDB: 3B6A) contains both a ligand-binding (bottom half) and a more conserved DNA-binding domain (top half). (B) The ring-shaped pentameric B-subunit of a shiga-like toxin (PDB: 1CQF) binds globotriaosylceramide (Gb3) via a relatively flat interface that surrounds the center of the ring. (C) The carbohydrate binding sites of the CBM29 protein (PDB: 1GWL) are too long and flat to be detected by ConCavity in the presence of a concave pocket between the chains. As illustrated here, ConCavity's inaccurate predictions are often the result of misleading evolutionary sequence conservation information (A) or ligands that bind partially or entirely outside of well-defined concave surface pockets (B, C). In (A) and (B), ConCavity misses the ligands, but identifies functionally relevant binding sites for other types of interactions (DNA and protein).