Peptide conformational preferences in osmolyte solutions: Transfer free energies of decaalanine

Hironori Kokubo, Char Y. Hu, B. Montgomery Pettitt

Research output: Contribution to journalArticlepeer-review

102 Scopus citations


The nature in which the protecting osmolyte trimethylamine N-oxide (TMAO) and the denaturing osmolyte urea affect protein stability is investigated, simulating a decaalanine peptide model in multiple conformations of the denatured ensemble. Binary solutions of both osmolytes and mixed osmolyte solutions at physiologically relevant concentrations of 2:1 (urea:TMAO) are studied using standard molecular dynamics simulations and solvation free energy calculations. Component analysis reveals the differences in the importance of the van der Waals (vdW) and electrostatic interactions for protecting and denaturing osmolytes. We find that urea denaturation governed by transfer free energy differences is dominated by vdW attractions, whereas TMAO exerts its effect by causing unfavorable electrostatic interactions both in the binary solution and mixed osmolyte solution. Analysis of the results showed no evidence in the ternary solution of disruption of the correlations among the peptide and osmolytes, nor of significant changes in the strength of the water hydrogen bond network.

Original languageEnglish (US)
Pages (from-to)1849-1858
Number of pages10
JournalJournal of the American Chemical Society
Issue number6
StatePublished - Feb 16 2011
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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