title: Optimal docking area: a new method for predicting protein-protein interaction sites.
abstract: Understanding energetics and mechanism of protein-protein association remains one of the biggest theoretical problems in structural biology. It is assumed that desolvation must play an essential role during the association process, and indeed protein-protein interfaces in obligate complexes have been found to be highly hydrophobic. However, the identification of protein interaction sites from surface analysis of proteins involved in non-obligate protein-protein complexes is more challenging. Here we present Optimal Docking Area (ODA), a new fast and accurate method of analyzing a protein surface in search of areas with favorable energy change when buried upon protein-protein association. The method identifies continuous surface patches with optimal docking desolvation energy based on atomic solvation parameters adjusted for protein-protein docking. The procedure has been validated on the unbound structures of a total of 66 non-homologous proteins involved in non-obligate protein-protein hetero-complexes of known structure. Optimal docking areas with significant low-docking surface energy were found in around half of the proteins. The 'ODA hot spots' detected in X-ray unbound structures were correctly located in the known protein-protein binding sites in 80% of the cases. The role of these low-surface-energy areas during complex formation is discussed. Burial of these regions during protein-protein association may favor the complexed configurations with near-native interfaces but otherwise arbitrary orientations, thus driving the formation of an encounter complex. The patch prediction procedure is freely accessible at http://www.molsoft.com/oda and can be easily scaled up for predictions in structural proteomics.
authors.affiliation: Department of Molecular Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Fernandez-Recio
authors.forename: Max
authors.initials: M
authors.lastname: Totrov
authors.forename: Constantin
authors.initials: C
authors.lastname: Skorodumov
authors.forename: Ruben
authors.initials: R
authors.lastname: Abagyan
mesh_terms: D001665:Binding Sites / Q000502:physiology; D003198:Computer Simulation; D030562:Databases, Protein; D008958:Models, Molecular; D011237:Predictive Value of Tests; D025941:Protein Interaction Mapping / Q000379:methods*; D017434:Protein Structure, Tertiary / Q000502:physiology; D013499:Surface Properties