Evaluation of Protein Docking Predictions Using Hex 3.1 in CAPRI Rounds 1 and 2

David William Ritchie

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

This article describes and reviews our efforts using Hex 3.1 to predict the docking modes of the seven target protein-protein complexes presented in the CAPRI (Critical Assessment of Predicted Interactions) blind docking trial. For each target, the structure of at least one of the docking partners was given in its unbound form, and several of the targets involved large multimeric structures (e.g., Lactobacillus HPr kinase, hemagglutinin, bovine rotavirus VP6). Here we describe several enhancements to our original spherical polar Fourier docking correlation algorithm. For example, a novel surface sphere smothering algorithm is introduced to generate multiple local coordinate systems around the surface of a large receptor molecule, which may be used to define a small number of initial ligand-docking orientations distributed over the receptor surface. High-resolution spherical polar docking correlations are performed over the resulting receptor surface patches, and candidate docking solutions are refined by using a novel soft molecular mechanics energy minimization procedure. Overall, this approach identified two good solutions at rank 5 or less for two of the seven CAPRI complexes. Subsequent analysis of our results shows that Hex 3.1 is able to place good solutions within a list of :520 for four of the seven targets. This finding shows that useful in silico protein-protein docking predictions can now be made with increasing confidence, even for very large macromolecular complexes. (C) 2003 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)98-106
Number of pages8
JournalProteins: Structure, Function, and Bioinformatics
Volume52
Issue number1
Early online date14 May 2003
DOIs
Publication statusPublished - Jul 2003

Keywords

  • blind docking trial
  • protein shape
  • shape complementarity
  • Fourier correlation
  • fast Fourier transform
  • spherical harmonics
  • OPLS potentials
  • pancreatic alpha-amylase
  • X-Ray structure
  • crystal-structure
  • beta-chain
  • binding
  • receptor
  • HPR
  • electrostatics
  • hemagglutinin

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