Heterogeneity even at the speed limit of folding: large-scale molecular dynamics study of a fast-folding variant of the villin headpiece.

ABSTRACT: We have performed molecular dynamics simulations on a set of nine unfolded conformations of the fastest-folding protein yet discovered, a variant of the villin headpiece subdomain (HP-35 NleNle). The simulations were generated using a new distributed computing method, yielding hundreds of trajectories each on a time scale comparable to the experimental folding time, despite the large (10,000 atom) size of the simulation system. This strategy eliminates the need to assume a two-state kinetic model or to build a Markov state model. The relaxation to the folded state at 300 K from the unfolded configurations (generated by simulation at 373 K) was monitored by a method intended to reflect the experimental observable (quenching of tryptophan by histidine). We also monitored the relaxation to th

SUBMITTER: Ensign DL 

PROVIDER: S-EPMC3689540 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature