title: A simple reference state makes a significant improvement in near-native selections from structurally refined docking decoys.
abstract: Near-native selections from docking decoys have proved challenging especially when unbound proteins are used in the molecular docking. One reason is that significant atomic clashes in docking decoys lead to poor predictions of binding affinities of near native decoys. Atomic clashes can be removed by structural refinement through energy minimization. Such an energy minimization, however, will lead to an unrealistic bias toward docked structures with large interfaces. Here, we extend an empirical energy function developed for protein design to protein-protein docking selection by introducing a simple reference state that removes the unrealistic dependence of binding affinity of docking decoys on the buried solvent accessible surface area of interface. The energy function called EMPIRE (EMpirical Protein-InteRaction Energy), when coupled with a refinement strategy, is found to provide a significantly improved success rate in near native selections when applied to RosettaDock and refined ZDOCK docking decoys. Our work underlines the importance of removing nonspecific interactions from specific ones in near native selections from docking decoys.
authors.affiliation: Howard Hughes Medical Institute Center for Single Molecule Biophysics, Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Shide
authors.initials: S
authors.lastname: Liang
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Yaoqi
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D001665:Binding Sites / Q000502:physiology; D003198:Computer Simulation; D016014:Linear Models; D008958:Models, Molecular; D011485:Protein Binding / Q000502:physiology; D025941:Protein Interaction Mapping / Q000592:standards*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D012015:Reference Standards; D013816:Thermodynamics
chemical_list: D011506:Proteins