Perspective: Alchemical free energy calculations for drug discovery.

ABSTRACT: Computational techniques see widespread use in pharmaceutical drug discovery, but typically prove unreliable in predicting trends in protein-ligand binding. Alchemical free energy calculations seek to change that by providing rigorous binding free energies from molecular simulations. Given adequate sampling and an accurate enough force field, these techniques yield accurate free energy estimates. Recent innovations in alchemical techniques have sparked a resurgence of interest in these calculations. Still, many obstacles stand in the way of their routine application in a drug discovery context, including the one we focus on here, sampling. Sampling of binding modes poses a particular challenge as binding modes are often separated by large energy barriers, leading to slow transitions. Bindi

SUBMITTER: Mobley DL 

PROVIDER: S-EPMC3537745 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature