Integrative Geometric-Hashing Approaches to Binding Site Modeling and Ligand-Protein Interaction Prediction

The function of a protein is dependent on whether and how it can interact with various ligands. Therefore, an accurate prediction of protein-ligand interactions is paramount to understanding proteins’ biological mechanisms and hence to the development of therapeutic agents. A ligand is most likely to bind in the largest pocket on the surface of the protein. Moreover, it requires that the pocket meets certain structural and geometric criteria that allow the ligand to “anchor” in place by forming stabilizing interactions with the protein. Based on this logic, many geometry-based algorithms have been developed to predict protein-ligand interactions. Here we investigate a geometric-hashing based algorithm – to see how well it distinguishes proteins that do and do not bind a ligand, and propose enhancements that improve its robustness. We also introduce an alternative way of integrating geometric and biochemical properties of multiple binding mechanisms into a single representation.