A highly accurate metadynamics-based Dissociation Free Energy method to calculate protein-protein and protein-ligand binding potencies.

ABSTRACT: Although seeking to develop a general and accurate binding free energy calculation method for protein-protein and protein-ligand interactions has been a continuous effort for decades, only limited successes have been obtained so far. Here, we report the development of a metadynamics-based procedure that calculates Dissociation Free Energy (DFE) and its application to 19 non-congeneric protein-protein complexes and hundreds of protein-ligand complexes covering eight targets. We achieved very high correlations in comparison to experimental binding free energies for these diverse sets of systems, demonstrating the generality and accuracy of the method. Since structures of most proteins are available owing to the recent success of prediction by artificial intelligence, a general free energy me

SUBMITTER: Wang J 

PROVIDER: S-EPMC8821539 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature