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
, which compares well with
the experimental value.
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, which compares well with
the experimental value.
