Heterogeneous path ensembles for conformational transitions in semi-atomistic models of adenylate kinase.

We performed "weighted ensemble" path-sampling simulations of adenylate kinase, using several semi-atomistic protein models. The models have an all-atom backbone with various levels of residue interactions. The primary result is that full statistically rigorous path sampling required only a few weeks of single-processor computing time with these models, indicating the addition of further chemical detail should be readily feasible. Our semi-atomistic path ensembles are consistent with previous biophysical findings: the presence of two distinct pathways, identification of intermediates, and symmetry of forward and reverse pathways.