This Article Full Text Full Text (PDF) Supplement All Versions of this Article: biophysj.107.108290v1 93/1/L04    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mason, P. E. Articles by Dempsey, C. E. Search for Related Content PubMed PubMed Citation Articles by Mason, P. E. Articles by Dempsey, C. E.

The Interaction of Guanidinium Ions with a Model Peptide

Philip E. Mason ^*, John W. Brady ^*, George W. Neilson  and Christopher E. Dempsey 

^* Department of Food Sciences, Stocking Hall, Cornell University, Ithaca, New York; and H.H. Wills Physics Laboratory, Department of Biochemistry, University of Bristol, Bristol, United Kingdom

Correspondence: Address reprint requests and inquiries to Chris Dempsey, Tel.: 44-117-928-7427; E-mail: c.dempsey{at}bris.ac.uk, or John Brady, Tel.: 607-255-2897; E-mail: jwb7{at}cornell.edu.

In addition to promoting unfolded protein states, the denaturants urea and guanidinium (Gdm⁺) accumulate at the surface of folded proteins at subdenaturing concentrations, a phenomenon that correlates with their denaturant activities. The enhanced accumulation of Gdm⁺ relative to urea indicates different binding modes, or additional binding sites, for Gdm⁺, and we recently proposed potential binding modes to protein functional groups for Gdm⁺ based on the determination of the weak hydration properties of this complex cation. Here we describe molecular dynamics simulations of a model helical peptide, melittin, in a 3 M solution of GdmCl, to identify potential interactions with amino-acid side chains in a nondenatured polypeptide surface. The simulations indicate that Gdm⁺ can interact with a number of planar amino-acid side chains (Arg, Trp, Gln) in a stacking manner, as well as more weakly with hydrophobic surfaces composed of aliphatic side chains, and that these interactions result in enhanced number densities of Gdm⁺ at certain locations on the peptide surface. These observations provide molecular scale insight into the accumulation of Gdm⁺ at protein surfaces that has previously been observed experimentally.

This article has been cited by other articles:

				C. Camilloni, A. G. Rocco, I. Eberini, E. Gianazza, R. A. Broglia, and G. Tiana Urea and Guanidinium Chloride Denature Protein L in Different Ways in Molecular Dynamics Simulations Biophys. J., June 15, 2008; 94(12): 4654 - 4661. [Abstract] [Full Text] [PDF]