The Interaction of Guanidinium Ions With a Model Peptide
Philip E Mason 1, John W Brady 1, George W Neilson 2 and Christopher E Dempsey 3*
1 Cornell University
2 Physics Department, Bristol University
3 Biochemistry Department, Bristol University
* To whom correspondence should be addressed. E-mail: c.dempsey{at}bris.ac.uk.
Submitted on March 7, 2007
Revised on March 22, 2007
Accepted on 17 April 2007
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Abstract |
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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 3M solution of GdmCl, to identify potential interactions with amino acid side chains in a non-denatured 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.
Key Words:
dynamics simulation, melittin, protein denaturation, solvation
