Relative Binding Free Energy Calculations Applied to Protein Homology Models.

ABSTRACT: A significant challenge and potential high-value application of computer-aided drug design is the accurate prediction of protein-ligand binding affinities. Free energy perturbation (FEP) using molecular dynamics (MD) sampling is among the most suitable approaches to achieve accurate binding free energy predictions, due to the rigorous statistical framework of the methodology, correct representation of the energetics, and thorough treatment of the important degrees of freedom in the system (including explicit waters). Recent advances in sampling methods and force fields coupled with vast increases in computational resources have made FEP a viable technology to drive hit-to-lead and lead optimization, allowing for more efficient cycles of medicinal chemistry and the possibility to explore mu

SUBMITTER: Cappel D 

PROVIDER: S-EPMC5777225 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature