The dominant interaction between peptide and urea is electrostatic in nature: A molecular dynamics simulation study

Dror Tobi, Ron Elber, Devarajan Thirumalai

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

The conformational equilibrium of a blocked valine peptide in water and aqueous urea solution is studied using molecular dynamics simulations. Pair correlation functions indicate enhanced concentration of urea near the peptide. Stronger hydrogen bonding of urea-peptide compared to water-peptide is observed with preference for helical conformation. The potential of mean force, computed using umbrella sampling, shows only small differences between urea and water solvation that are difficult to quantify. The changes in solvent structure around the peptide are explained by favorable electrostatic interactions (hydrogen bonds) of urea with the peptide backbone. There is no evidence for significant changes in hydrophobic interactions in the two conformations of the peptide in urea solution. Our simulations suggest that urea denatures proteins by preferentially forming hydrogen bonds to the peptide backbone, reducing the barrier for exposing protein residues to the solvent, and reaching the unfolded state.

Original languageEnglish
Pages (from-to)359-369
Number of pages11
JournalBiopolymers
Volume68
Issue number3
DOIs
StatePublished - Mar 2003
Externally publishedYes

Keywords

  • Computer simulations
  • Denaturation
  • Electrostatic interactions
  • Hydrophobicity
  • Potential of mean force
  • Unfolding

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