Backbone additivity in the transfer model of protein solvation

Char Y. Hu, Hironori Kokubo, Gillian C. Lynch, D. Wayne Bolen, Bernard Pettitt

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62 Scopus citations

Abstract

The transfer model implying additivity of the peptide backbone free energy of transfer is computationally tested. Molecular dynamics simulations are used to determine the extent of change in transfer free energy (ΔG tr) with increase in chain length of oligoglycine with capped end groups. Solvation free energies of oligoglycine models of varying lengths in pure water and in the osmolyte solutions, 2M urea and 2M trimethylamine N-oxide (TMAO), were calculated from simulations of all atom models, and ΔG tr values for peptide backbone transfer from water to the osmolyte solutions were determined. The results show that the transfer free energies change linearly with increasing chain length, demonstrating the principle of additivity, and provide values in reasonable agreement with experiment. The peptide backbone transfer free energy contributions arise from van der Waals interactions in the case of transfer to urea, but from electrostatics on transfer to TMAO solution. The simulations used here allow for the calculation of the solvation and transfer free energy of longer oligoglycine models to be evaluated than is currently possible through experiment. The peptide backbone unit computed transfer free energy of -54 cal/mol/M compares quite favorably with -43 cal/mol/M determined experimentally. Published by Wiley-Blackwell.

Original languageEnglish (US)
Pages (from-to)1011-1022
Number of pages12
JournalProtein Science
Volume19
Issue number5
DOIs
StatePublished - May 2010
Externally publishedYes

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Keywords

  • Backbone solvation
  • Folding
  • Free energy
  • Glycine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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