Multiple Ligand Unbinding Pathways and Ligand-Induced Destabilization Revealed by WExplore.

ABSTRACT: We report simulations of full ligand exit pathways for the trypsin-benzamidine system, generated using the sampling technique WExplore. WExplore is able to observe millisecond-scale unbinding events using many nanosecond-scale trajectories that are run without introducing biasing forces. The algorithm generates rare events by dividing the coordinate space into regions, on-the-fly, and balancing computational effort between regions through cloning and merging steps, as in the weighted ensemble method. The averaged exit flux yields a ligand exit rate of 180 μs, which is within an order of magnitude of the experimental value. We obtain broad sampling of ligand exit pathways, and visualize our findings using conformation space networks. The analysis shows three distinct exit channels, two of w

SUBMITTER: Dickson A 

PROVIDER: S-EPMC5340210 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature