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Biophys. J. BioFAST: First Published May 20, 2005. doi:10.1529/biophysj.105.061978
© 2005 by the Biophysical Society.

A more recent version of this article appeared on August 1, 2005.
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BIOPHYSICAL THEORY AND MODELING

EFFECT OF UREA ON PEPTIDE CONFORMATION IN WATER: MOLECULAR DYNAMICS AND EXPERIMRENTAL CHARACTERIZATION

Ana Caballero-Herrera 1, Kerstin Nordstrand 2, Kurt D Berndt 3 and Lennart Nilsson 1*

1 Karolinska Institutet
2 Södertörns högskola
3 Karolinska Institutet, Södertörns högskola

* To whom correspondence should be addressed. E-mail: lennart.nilsson{at}biosci.ki.se.

Submitted on March 1, 2005
Revised on April 11, 2005
Accepted on 6 May 2005


  Abstract
Molecular dynamics simulations of a ribonuclease A C-peptide analogue and a sequence variant were performed in water at 277 and 300 K and in 8M urea to clarify the molecular denaturation mechanism induced by urea and the early events in protein unfolding. Spectroscopic characterization of the peptides showed that the C-peptide analogue had a high {alpha}-helical content, which was not the case for the variant. In the simulations, interdependent side chain interactions were responsible for the high stability of the {alpha}-helical C-peptide analogue in the different solvents. The other peptide displayed {alpha}-helical unwinding that propagated cooperatively towards the N-terminal. The conformations sampled by the peptides depended on their sequence and on the solvent. The ability of water molecules to form hydrogen bonds to the peptide as well as the hydrogen bond lifetimes increased in the presence of urea, whereas water mobility was reduced near the peptide. Urea accumulated in excess around the peptide, to which it formed long-lived hydrogen bonds. The unfolding mechanisms induced by thermal denaturation and by urea are of different nature, with urea-aqueous solutions providing a better peptide solvation than pure water. Our results suggest that the effect of urea on the chemical denaturation process involves both the direct and indirect mechanisms.

Key Words: alpha helix, hydrogen bonds, simulation




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Copyright © 2005 by the Biophysical Society.