The effect of motional averaging on the calculation of NMR-derived structural properties

The effect of motional averaging when relating structural properties inferr ed from nuclear magnetic resonance (NMR) experiments to molecular dynamics simulations of peptides is considered. In particular, the effect of changin g populations of conformations, the extent of sampling, and the sampling fr equency on the estimation of nuclear Overhauser effect (NOE) inter-proton d istances, vicinal (3)J-coupling constants, and chemical shifts are investig ated. The analysis is based on 50-ns simulations of a beta-heptapeptide in methanol at 298 K, 340 K, 350 K, and 360 K, This peptide undergoes reversib le folding and samples a significant proportion of the available conformati onal space during the simulations, with at 298 K being predominantly folded and at 360 K being predominantly unfolded, The work highlights the fact th at when motional averaging is included, NMR data has only limited capacity to distinguish between a single fully folded peptide conformation and vario us mixtures of folded and unfolded conformations. Proteins 1999;36:542-555. (C) 1999 Wiley-Liss, Inc.