Reaction Coordinate-Free Approach to Recovering Kinetics from Potential-Scaled Simulations: Application of Kramers’ Rate Theory

Enhanced sampling techniques are used to increase the frequency of “rare events” during computer simulations of complex molecules. Although methods exist that allow accurate thermodynamics to be recovered from enhanced simulations, recovering kinetics proves to be more challenging. Here we present an extrapolation approach that allows reliable kinetics to be recovered from potential-scaled MD simulations. The approach, based on Kramers’ rate theory, is simple and computationally efficient, and allows kinetics to be recovered without defining reaction coordinates. To test our approach, we use it to determine the kinetics of barrier crossing between two metastable states on the 2D-Müller potential and the C 7eq to α R transition in alanine dipeptide. The mean first passage time estimates obtained are in excellent agreement with reference values obtained from direct simulations on the unscaled potentials performed over times that are orders of magnitude longer.