A library of protein surface patches discriminates between native structures and decoys generated by structure prediction servers

Background: Protein surfaces serve as an interface with the molecular environment and are thus tightly bound to protein function. On the surface, geometric and chemical complementarity to other molecules provides interaction specificity for ligand binding, docking of bio-macromolecules, and enzymatic catalysis. As of today, there is no accepted general scheme to represent protein surfaces. Furthermore, most of the research on protein surface focuses on regions of specific interest such as interaction, ligand binding, and docking sites. We present a first step toward a general purpose representation of protein surfaces: a novel surface patch library that represents most surface patches (∼98%) in a data set regardless of their functional roles. Results: Surface patches, in this work, are small fractions of the protein surface. Using a measure of inter-patch distance, we clustered patches extracted from a data set of high quality, non-redundant, proteins. The surface patch library is the collection of all the cluster centroids; thus, each of the data set patches is close to one of the elements in the library. We demonstrate the biological significance of our method through the ability of the library to capture surface characteristics of native protein structures as opposed to those of decoy sets generated by state-of-the-art protein structure prediction methods. The patches of the decoys are significantly less compatible with the library than their corresponding native structures, allowing us to reliably distinguish native models from models generated by servers. This trend, however, does not extend to the decoys themselves, as their similarity to the native structures does not correlate with compatibility with the library. Conclusions: We expect that this high-quality, generic surface patch library will add a new perspective to the description of protein structures and improve our ability to predict them. In particular, we expect that it will help improve the prediction of surface features that are apparently neglected by current techniques. The surface patch libraries are publicly available at http://www.cs.bgu.ac.il/∼keasar/ patchLibrary.