Refining the treatment of membrane proteins by coarse-grained models

Igor Vorobyov, Ilsoo Kim, Zhen T. Chu, Arieh Warshel

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Obtaining a quantitative description of the membrane proteins stability is crucial for understanding many biological processes. However the advance in this direction has remained a major challenge for both experimental studies and molecular modeling. One of the possible directions is the use of coarse-grained models but such models must be carefully calibrated and validated. Here we use a recent progress in benchmark studies on the energetics of amino acid residue and peptide membrane insertion and membrane protein stability in refining our previously developed coarse-grained model (Vicatos et al., Proteins 2014;82:1168). Our refined model parameters were fitted and/or tested to reproduce water/membrane partitioning energetics of amino acid side chains and a couple of model peptides. This new model provides a reasonable agreement with experiment for absolute folding free energies of several β-barrel membrane proteins as well as effects of point mutations on a relative stability for one of those proteins, OmpLA. The consideration and ranking of different rotameric states for a mutated residue was found to be essential to achieve satisfactory agreement with the reference data.

Original languageEnglish (US)
Pages (from-to)92-117
Number of pages26
JournalProteins: Structure, Function and Bioinformatics
Volume84
Issue number1
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Keywords

  • Arginine
  • Folding energy
  • Ion-induced defect
  • Lipid membrane
  • Membrane electrostatics
  • Molecular modeling
  • Mutation
  • OmpLA
  • Partitioning free energy
  • Rotamer

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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