Force-field dependence of chignolin folding and misfolding: comparison with experiment and redesign.

ABSTRACT: We study the folding of the designed hairpin chignolin, using simulations with four different force fields. Interestingly, we find a misfolded, out-of-register, structure comprising 20-50% of the ordered structures with three force fields, but not with a fourth. A defining feature of the misfold is that Gly-7 adopts a β(PR) conformation rather than α(L). By reweighting, we show that differences between the force fields can mostly be attributed to differences in glycine properties. Benchmarking against NMR data suggests that the preference for β(PR) is not a force-field artifact. For chignolin, we show that including the misfold in the ensemble results in back-recalculated NMR observables in slightly better agreement with experiment than parameters calculated from a folded ensemble only. Fo

SUBMITTER: Kuhrova P 

PROVIDER: S-EPMC3328722 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature