Expanded Ensemble Methods Can be Used to Accurately Predict Protein-Ligand Relative Binding Free Energies.

ABSTRACT: Alchemical free energy methods have become indispensable in computational drug discovery for their ability to calculate highly accurate estimates of protein-ligand affinities. Expanded ensemble (EE) methods, which involve single simulations visiting all of the alchemical intermediates, have some key advantages for alchemical free energy calculation. However, there have been relatively few examples published in the literature of using expanded ensemble simulations for free energies of protein-ligand binding. In this paper, as a test of expanded ensemble methods, we compute relative binding free energies using the Open Force Field Initiative force field (codename "Parsley") for 24 pairs of Tyk2 inhibitors derived from a congeneric series of 16 compounds. The EE predictions agree well with th

SUBMITTER: Zhang S 

PROVIDER: S-EPMC9333416 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature