  We performed "weighted ensemble" path-sampling simulations of adenylate
kinase, using several semi-atomistic protein models. Our study investigated
both the biophysics of conformational transitions as well as the possibility of
increasing model accuracy without sacrificing good sampling. Biophysically, the
path ensembles show significant heterogeneity and the explicit possibility of
two principle pathways in the Open-Closed transition. We recently showed, under
certain conditions, a "symmetry of hetereogeneity" is expected between the
forward and the reverse transitions: the fraction of transitions taking a
specific pathway/channel will be the same in both the directions. Our path
ensembles are analyzed in the light of the symmetry relation and its
conditions. In the realm of modeling, we employed an all-atom backbone with
various levels of residue interactions. Because reasonable path sampling
required only a few weeks of single-processor computing time with these models,
the addition of further chemical detail should be feasible.
