Protein structure refinement with adaptively restrained homologous replicas

Proteins. 2016 Sep:84 Suppl 1:302-13. doi: 10.1002/prot.24939. Epub 2015 Oct 27.

Abstract

A novel protein refinement protocol is presented which utilizes molecular dynamics (MD) simulations of an ensemble of adaptively restrained homologous replicas. This approach adds evolutionary information to the force field and reduces random conformational fluctuations by coupling of several replicas. It is shown that this protocol refines the majority of models from the CASP11 refinement category and that larger conformational changes of the starting structure are possible than with current state of the art methods. The performance of this protocol in the CASP11 experiment is discussed. We found that the quality of the refined model is correlated with the structural variance of the coupled replicas, which therefore provides a good estimator of model quality. Furthermore, some remarkable refinement results are discussed in detail. Proteins 2016; 84(Suppl 1):302-313. © 2015 Wiley Periodicals, Inc.

Keywords: CASP11; homology modeling; molecular dynamics simulation; structure refinement.

MeSH terms

  • Algorithms
  • Amino Acid Motifs
  • Benchmarking
  • Computational Biology / methods
  • Computational Biology / statistics & numerical data*
  • Humans
  • Internet
  • Models, Statistical*
  • Molecular Dynamics Simulation*
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Folding
  • Protein Interaction Domains and Motifs
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Sequence Homology, Amino Acid
  • Software*
  • Thermodynamics

Substances

  • Proteins