Trimethylamine N-oxide influence on the backbone of proteins: An oligoglycine model

Char Y. Hu, Gillian C. Lynch, Hironori Kokubo, B. Montgomery Pettitt

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

The study of organic osmolytes has been pivotal in demonstrating the role of solvent effects on the protein backbone in the folding process. Although a thermodynamic description of the interactions between the protein backbone and osmolyte has been well defined, the structural analysis of the effect of osmolyte on the protein backbone has been incomplete. Therefore, we have performed simulations of a peptide backbone model, glycine,5, in protecting osmolyte trimethylamine Noxide (TMAO) solution, in order to determine the effect of the solution structure on the conformation of the peptide backbone. We show that the models chosen show that the ensemble of backbone structures shifts toward a more collapsed state in TMAO solution as compared with pure water solution. The collapse is consistent with preferential exclusion of the osmolyte caused by unfavorable interactions between osmolyte and peptide backbone. The exclusion is caused by strong triplet correlations of osmolyte, water, and peptide backbone. This provides a clear mechanism showing that even a modest concentration of TMAO forces the protein backbone to adopt a more collapsed structure in the absence of side chain effects.

Original languageEnglish (US)
Pages (from-to)695-704
Number of pages10
JournalProteins: Structure, Function and Bioinformatics
Volume78
Issue number3
DOIs
StatePublished - Apr 28 2010

Keywords

  • Osmolyte
  • Protein folding
  • Solvation

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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