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A simple reference state makes a significant improvement in near‐native selections from structurally refined docking decoys
Author(s) -
Liang Shide,
Liu Song,
Zhang Chi,
Zhou Yaoqi
Publication year - 2007
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21498
Subject(s) - docking (animal) , macromolecular docking , searching the conformational space for docking , energy minimization , computer science , minification , chemistry , binding site , molecular dynamics , computational chemistry , biochemistry , medicine , programming language , nursing
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. Proteins 2007. © 2007 Wiley‐Liss, Inc.