Bimolecular reaction simulation using Weighted Ensemble Brownian dynamics and the University of Houston Brownian Dynamics program

We discuss here the implementation of the Weighted Ensemble Brownian (WEB) dynamics algorithm of Huber and Kim in the University of Houston Brownian D ynamics (UHBD) suite of programs and its application to bimolecular associa tion problems. WEB dynamics is a biased Brownian dynamics (BD) algorithm th at is more efficient than the standard Northrup-Allison-McCammon (NAM) meth od in cases where reaction events are infrequent because of intervening fre e energy barriers. Test cases reported here include the Smoluchowski rate f or association of spheres, the association of the enzyme copper-zinc supero xide dismutase with superoxide anion, and the binding of the superpotent sw eetener N-(p-cyanophenyl)-N'-(diphenylmethyl)-guanidinium acetic acid to a monoclonal antibody fragment, NC6.8. Our results show that the WEB dynamics algorithm is a superior simulation method for enzyme-substrate reaction en counters with large free energy barriers.