Abstract
It has long been known that a protein's amino acid sequence dictates
its native structure. However, despite significant recent advances, an
ensemble description of how a protein achieves its native conformation
from random coil under physiologically relevant conditions remains
incomplete. Here we present a detailed all-atom model with a
transferable potential that is capable of ab initio folding of entire
protein domains using only sequence information. The computational
efficiency of this model allows us to perform thousands of
microsecond-time scale-folding simulations of the engrailed homeodomain
and to observe thousands of complete independent folding events. We
apply a graph-theoretic analysis to this massive data set to elucidate
which intermediates and intermediary states are common to many
trajectories and thus important for the folding process. This method
provides an atomically detailed and complete picture of a folding
pathway at the ensemble level. The approach that we describe is quite
general and could be used to study the folding of proteins on time
scales orders of magnitude longer than currently possible.
Users
Please
log in to take part in the discussion (add own reviews or comments).