Multiple Conformations of RGDW anddRGDW: A Theoretical Study and Comparison with NMR Results

Abstract

The utility of molecular dynamics simulations in complementing limited NMR data for small peptides is demonstrated by an application to the important cell adhesion peptide Arg-Gly-Asp-Trp (RGDW) and its synthetic analogue, d-Arg-Gly-Asp-Trp (d-RGDW). The results of an earlier NMR study of these peptides were interpreted in terms of a type II‘ β-turn conformation (Kieffer, B.; Mer, G.; Mann, A.; Lefevre, J. F. Int. J. Pept. Protein Res. 1994, 44, 70−79). The present simulations provide additional insight into the solution structure of the RGDW and d-RGDW peptides by identifying extended conformations of both peptides in aqueous solution that are also compatible with the NMR data. The extended conformations have similar values for the NMR observables as the type II‘ β-turn, including the pH titration behavior, coupling constants, ROESY proton distances and pKa values of the Asp side chain and the C-terminal end. Thus it is difficult to distinguish the two conformations by NMR alone. Poisson−Boltzmann contin...