TCB Publications - Abstract

Ivan Teo, Christopher G. Mayne, Klaus Schulten, and Tony Lelievre. Adaptive multilevel splitting method for molecular dynamics calculation of benzamidine-trypsin dissociation time. Journal of Chemical Theory and Computation, 12:2983-2989, 2016.

TEO2016 Adaptive Multilevel Splitting (AMS) is a rare event sampling method that requires minimal parameter tuning and that allows unbiased sampling of transition pathways of a given rare event. Previous simulation studies have verified the efficiency and accuracy of AMS in the calculation of transition times for simple systems in both Monte Carlo and molecular dynamics (MD) simulations. Now, AMS is applied for the first time to a MD simulation of protein-ligand dissociation, representing a leap in complexity from the previous test cases. Of interest is the dissociation rate, which is typically too low to be accessible to conventional MD. The present study joins other recent efforts to develop advanced sampling techniques in MD to calculate dissociation rates, which are gaining importance in the pharmaceutical field as indicators of drug efficacy. The system investigated here, benzamidine bound to trypsin, is an example common to many of these efforts. The AMS estimate of the dissociation rate was found to be $(2.6\pm 2.4)\times 10^2~\textrm{s}^{-1}$, which compares well with the experimental value.

Download Full Text

The manuscripts available on our site are provided for your personal use only and may not be retransmitted or redistributed without written permissions from the paper's publisher and author. You may not upload any of this site's material to any public server, on-line service, network, or bulletin board without prior written permission from the publisher and author. You may not make copies for any commercial purpose. Reproduction or storage of materials retrieved from this web site is subject to the U.S. Copyright Act of 1976, Title 17 U.S.C.

Download full text: Request a Copy, Journal