SURFCOMP: A Novel Graph‐Based Approach to Molecular Surface Comparison.

Abstract

Analysis of the distributions of physicochemical properties mapped onto molecular surfaces can highlight important similarities or differences between compound classes, contributing to rational drug design efforts. Here we present an approach that uses maximal common subgraph comparison and harmonic shape image matching to detect locally similar regions between two molecular surfaces augmented with properties such as the electrostatic potential or lipophilicity. The complexity of the problem is reduced by a set of filters that implement various geometric and physicochemical heuristics. The approach was tested on dihydrofolate reductase and thermolysin inhibitors and was shown to recover the correct alignments of the compounds bound in the active sites.