Efficient estimation of transition rates as functions of pH

Abstract

Extracting the kinetic properties of a system whose dynamics depend on the pH of the environment with which it exchanges energy and atoms requires sampling the grand canonical ensemble. As an alternative, we present a novel strategy that requires simulating only the most recurrent canonical ensembles that compose the grand canonical ensemble. The simulations are used to estimate the grand canonical distribution for a specific pH value by reweighting and to construct the transition rate matrix by discretizing the Fokker–Planck equation by square root approximation and robust Perron cluster cluster analysis. As an application, we have studied the tripeptide Ala‐Asp‐Ala.