Comparison of Equilibrium and Nonequilibrium Approaches for Relative Binding Free Energy Predictions.

ABSTRACT: Alchemical relative binding free energy calculations have recently found important applications in drug optimization. A series of congeneric compounds are generated from a preidentified lead compound, and their relative binding affinities to a protein are assessed in order to optimize candidate drugs. While methods based on equilibrium thermodynamics have been extensively studied, an approach based on nonequilibrium methods has recently been reported together with claims of its superiority. However, these claims pay insufficient attention to the basis and reliability of both methods. Here we report a comparative study of the two approaches across a large data set, comprising more than 500 ligand transformations spanning in excess of 300 ligands binding to a set of 14 diverse protein target

SUBMITTER: Wan S 

PROVIDER: S-EPMC10653111 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature