The interaction of guanidinium ions with a model peptide.
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.
Mason
Philip E
PE
Department of Food Sciences, Stocking Hall, Cornell University, Ithaca, New York, USA.
Brady
John W
JW
Neilson
George W
GW
Dempsey
Christopher E
CE
D001665:Binding Sites; D003198:Computer Simulation; D019791:Guanidine / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D014867:Water / Q000737:chemistry
D010455:Peptides; D014867:Water; D019791:Guanidine