title: DARS (Decoys As the Reference State) potentials for protein-protein docking.
abstract: Decoys As the Reference State (DARS) is a simple and natural approach to the construction of structure-based intermolecular potentials. The idea is generating a large set of docked conformations with good shape complementarity but without accounting for atom types, and using the frequency of interactions extracted from these decoys as the reference state. In principle, the resulting potential is ideal for finding near-native conformations among structures obtained by docking, and can be combined with other energy terms to be used directly in docking calculations. We investigated the performance of various DARS versions for docking enzyme-inhibitor, antigen-antibody, and other type of complexes. For enzyme-inhibitor pairs, DARS provides both excellent discrimination and docking results, even with very small decoy sets. For antigen-antibody complexes, DARS is slightly better than a number of interaction potentials tested, but results are worse than for enzyme-inhibitor complexes. With a few exceptions, the DARS docking results are also good for the other complexes, despite poor discrimination, and we show that the latter is not a correct test for docking accuracy. The analysis of interactions in antigen-antibody pairs reveals that, in constructing pairwise potentials for such complexes, one should account for the asymmetry of hydrophobic patches on the two sides of the interface. Similar asymmetry does occur in the few other complexes with poor DARS docking results.
authors.affiliation: Department of Biomedical Engineering, and Program in Bioinformatics, Boston University, Boston, Massachusetts, USA.
authors.forename: Gwo-Yu
authors.initials: GY
authors.lastname: Chuang
authors.forename: Dima
authors.initials: D
authors.lastname: Kozakov
authors.forename: Ryan
authors.initials: R
authors.lastname: Brenke
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Comeau
authors.forename: Sandor
authors.initials: S
authors.lastname: Vajda
mesh_terms: D000936:Antigen-Antibody Complex; D004791:Enzyme Inhibitors / Q000378:metabolism; D004798:Enzymes / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding
chemical_list: D000936:Antigen-Antibody Complex; D004791:Enzyme Inhibitors; D004798:Enzymes