Monte Carlo replica-exchange based ensemble docking of protein conformations

Zhe Zhang, Uwe Ehmann, Martin Zacharias

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

A replica-exchange Monte Carlo (REMC) ensemble docking approach has been developed that allows efficient exploration of protein–protein docking geometries. In addition to Monte Carlo steps in translation and orientation of binding partners, possible conformational changes upon binding are included based on Monte Carlo selection of protein conformations stored as ordered pregenerated conformational ensembles. The conformational ensembles of each binding partner protein were generated by three different approaches starting from the unbound partner protein structure with a range spanning a root mean square deviation of 1–2.5 Å with respect to the unbound structure. Because MC sampling is performed to select appropriate partner conformations on the fly the approach is not limited by the number of conformations in the ensemble compared to ensemble docking of each conformer pair in ensemble cross docking. Although only a fraction of generated conformers was in closer agreement with the bound structure the REMC ensemble docking approach achieved improved docking results compared to REMC docking with only the unbound partner structures or using docking energy minimization methods. The approach has significant potential for further improvement in combination with more realistic structural ensembles and better docking scoring functions. Proteins 2017; 85:924–937.

Original languageEnglish
Pages (from-to)924-937
Number of pages14
JournalProteins: Structure, Function and Bioinformatics
Volume85
Issue number5
DOIs
StatePublished - 1 May 2017
Externally publishedYes

Keywords

  • advanced sampling simulations
  • protein complex formation
  • protein–protein interaction
  • receptor–ligand docking
  • replica exchange approaches

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