MD Simulations for D rug‐Target (Un)binding Kinetics

Protein–ligand (un)binding kinetics have been demonstrated to correlate better with drug efficacy than protein–ligand affinity. Consequently, the prediction of such kinetics via molecular dynamics simulations is of recent interest for pharmaceutical research. In this chapter, the theoretical basis for the calculation of such kinetics as well as biased molecular dynamics methods aiming for such predictions are introduced. The challenges involved in such predictions are highlighted and compared to binding affinity calculations. State-of-the-art of kinetics-predicting simulation methods are reviewed concerning both their capabilities and shortcomings.