Refining near-native protein-protein docking decoys by local resampling and energy minimization

Proteins. 2009 Aug 1;76(2):309-16. doi: 10.1002/prot.22343.

Abstract

How to refine a near-native structure to make it closer to its native conformation is an unsolved problem in protein-structure and protein-protein complex-structure prediction. In this article, we first test several scoring functions for selecting locally resampled near-native protein-protein docking conformations and then propose a computationally efficient protocol for structure refinement via local resampling and energy minimization. The proposed method employs a statistical energy function based on a Distance-scaled Ideal-gas REference state (DFIRE) as an initial filter and an empirical energy function EMPIRE (EMpirical Protein-InteRaction Energy) for optimization and re-ranking. Significant improvement of final top-1 ranked structures over initial near-native structures is observed in the ZDOCK 2.3 decoy set for Benchmark 1.0 (74% whose global rmsd reduced by 0.5 A or more and only 7% increased by 0.5 A or more). Less significant improvement is observed for Benchmark 2.0 (38% versus 33%). Possible reasons are discussed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Computational Biology
  • Databases, Protein
  • Models, Molecular
  • Protein Conformation
  • Protein Folding
  • Proteins / chemistry*
  • Proteins / metabolism
  • Thermodynamics*

Substances

  • Proteins