Molecular Simulation of Drug-Binding Kinetics

Early drug discovery often focuses on improving drug–receptor binding thermodynamics without considering drug-binding kinetics. This article first reviews some experiments and pathway simulations that point to the significance of considering drug-binding kinetics in drug discovery. It then describes our development and application of a molecular dynamics-based mining-minima approach to studying drug-binding kinetics, with the goal of aiding the design of drug candidates with certain desired binding kinetics. Discussions on further refinement of this approach with the Feynman path integral formalism then follow.