Roles of Accelerated Molecular Dynamics Simulations in Predictions of Binding Kinetic Parameters.

Rational predictions on binding kinetics parameters of drugs to targets play significant roles in future drug designs. Full conformational samplings of targets are requisite for accurate predictions of binding kinetic parameters. In this review, we mainly focus on the applications of enhanced sampling technologies in calculations of binding kinetics parameters and residence time of drugs. The methods involved in molecular dynamics simulations are applied to not only probe conformational changes of targets but also reveal calculations of residence time that is significant for drug efficiency. For this review, special attention are paid to accelerated molecular dynamics (aMD) and Gaussian aMD (GaMD) simulations that have been adopted to predict the association or disassociation rate constant. We also expect that this review can provide useful information for future drug design.