A simple reference state makes a significant improvement in near-native selections from structurally refined docking decoys

Shide Liang, Song Liu, Chi Zhang, Yaoqi Zhou

Research output: Contribution to journalArticle

43 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)244-253
Number of pages10
JournalProteins: Structure, Function and Genetics
Volume69
Issue number2
DOIs
StatePublished - Nov 1 2007
Externally publishedYes

Keywords

  • Binding affinity
  • Docking decoys
  • Energy score functions
  • Knowledge-based potential
  • Reference state

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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