Effect of local shape modifications of molecular surfaces on rigid-body protein-protein docking.

Abstract

Geometric complementarity is the most dominant term in protein-protein docking and therefore, a good geometric representation of the molecules, which takes into account the flexibility of surface residues, is desirable. We present a modified geometric representation of the molecular surface that down-weighs the contribution of specified parts of the surface to the complementarity score. We apply it to the mobile ends of the most flexible side chains: lysines, glutamines and arginines (trimming). The new representation systematically reduces the complementarity scores of the false-positive solutions, often more than the scores of the correct solutions, thereby improving significantly our ability to identify nearly correct solutions in rigid-body docking of unbound structures. The effect of trimming lysine residues is larger than trimming of glutamine or arginine residues. It appears to be independent of the conformations of the trimmed residues but depends on the relative abundance of such residues at the interface and on the non-interacting surface. Combining the modified geometric representation with electrostatic complementarity further improves the docking results.