While structural genomics resulted in thousands of new protein crystal structures, we still do not know the functions of most of these proteins. One reason for this shortcoming is their unique sequences or folds, which leaves them assigned as proteins of 'unknown function'. Recent advances in and applications of cutting edge binding site comparison algorithms for binding site detection and function prediction have begun to shed light on this problem.Since binding sites are usually more evolutionary conserved than the rest of the protein structure, binding site comparison enables finding functional relationships between evolutionarily distant proteins. Tools for binding site comparison range from those representing binding sites as fingerprints, to approaches that use geometric indexing, to graph theoretical approaches, where proteins are represented as vertices and edges. These tools open a whole new range of possibilities in drug discovery, and may circumvent some of the current limitations of virtual screening.Here, we review these algorithms and their use in function prediction and pharmaceutical discovery. Finding common binding sites in weakly related proteins may lead to the discovery of new protein functions and to novel ways of drug discovery.

Binding site prediction algorithms in pharmaceutical discovery

248th National Meeting (2014)

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