Peptide conformational preferences in osmolyte solutions

Transfer free energies of decaalanine

Hironori Kokubo, Char Y. Hu, Bernard Pettitt

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

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
Volume133
Issue number6
DOIs
StatePublished - Feb 16 2011
Externally publishedYes

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Energy Transfer
Peptides
Free energy
Urea
Coulomb interactions
Static Electricity
Oxides
Denaturation
Protein Stability
Solvation
Molecular Dynamics Simulation
Conformations
Molecular dynamics
Hydrogen
Hydrogen bonds
Proteins
Water
Computer simulation
trimethyloxamine

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Peptide conformational preferences in osmolyte solutions : Transfer free energies of decaalanine. / Kokubo, Hironori; Hu, Char Y.; Pettitt, Bernard.

In: Journal of the American Chemical Society, Vol. 133, No. 6, 16.02.2011, p. 1849-1858.

Research output: Contribution to journalArticle

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