The slow but steady rise of binding free energy calculations in drug discovery

Abstract

Binding free energy calculations are increasingly used in drug discovery research to predict protein-ligand binding affinities and to prioritize candidate drug molecules accordingly. It has taken decades of collective effort to transform this academic concept into a technology adopted by the pharmaceutical and biotech industry. Having personally witnessed and taken part in this transformation, here I recount the (incomplete) list of problems that had to be solved to make this computational tool practical and suggest areas of future development.

Keywords: Binding free energy; Computational drug discovery; Free energy perturbation; Simulations.