New approaches for computing ligand-receptor binding kinetics

Abstract

The recent and growing evidence that the efficacy of a drug can be correlated to target binding kinetics has seeded the development of a multitude of novel methods aimed at computing rate constants for receptor-ligand binding processes, as well as gaining an understanding of the binding and unbinding pathways and the determinants of structure-kinetic relationships. These new approaches include various types of enhanced sampling molecular dynamics simulations and the combination of energy-based models with chemometric analysis. We assess these approaches in the light of the varying levels of complexity of protein-ligand binding processes.