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Title: Peptide Conformational Preferences in Osmolyte Solutions: Transfer Free Energies of Decaalanine

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.

Authors:
; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
1028539
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Journal of the American Chemical Society
Additional Journal Information:
Journal Volume: 133; Journal Issue: 6; Journal ID: ISSN 0002-7863
Country of Publication:
United States
Language:
English
Subject:
08 HYDROGEN; ELECTROSTATICS; FREE ENERGY; HYDROGEN; PEPTIDES; PROTEINS; SOLVATION; STABILITY; UREA; WATER; Environmental Molecular Sciences Laboratory

Citation Formats

Kokubo, Hironori, Hu, Char Y, and Pettitt, Bernard M. Peptide Conformational Preferences in Osmolyte Solutions: Transfer Free Energies of Decaalanine. United States: N. p., 2011. Web. doi:10.1021/ja1078128.
Kokubo, Hironori, Hu, Char Y, & Pettitt, Bernard M. Peptide Conformational Preferences in Osmolyte Solutions: Transfer Free Energies of Decaalanine. United States. https://doi.org/10.1021/ja1078128
Kokubo, Hironori, Hu, Char Y, and Pettitt, Bernard M. 2011. "Peptide Conformational Preferences in Osmolyte Solutions: Transfer Free Energies of Decaalanine". United States. https://doi.org/10.1021/ja1078128.
@article{osti_1028539,
title = {Peptide Conformational Preferences in Osmolyte Solutions: Transfer Free Energies of Decaalanine},
author = {Kokubo, Hironori and Hu, Char Y and Pettitt, Bernard M},
abstractNote = {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.},
doi = {10.1021/ja1078128},
url = {https://www.osti.gov/biblio/1028539}, journal = {Journal of the American Chemical Society},
issn = {0002-7863},
number = 6,
volume = 133,
place = {United States},
year = {Wed Feb 16 00:00:00 EST 2011},
month = {Wed Feb 16 00:00:00 EST 2011}
}