On Calculating Free Energy Differences Using Ensembles of Transition Paths.

ABSTRACT: The free energy of a process is the fundamental quantity that determines its spontaneity or propensity at a given temperature. In particular, the binding free energy of a drug candidate to its biomolecular target is used as an objective quantity in drug design. Recently, binding kinetics-rates of association (k _on) and dissociation (k _off)-have also demonstrated utility for their ability to predict efficacy and in some cases have been shown to be more predictive than the binding free energy alone. Some methods exist to calculate binding kinetics from molecular simulations, although these are typically more difficult to calculate than the binding affinity as they depend on details of the transition path ensemble. Assessing these rate constants can be diff

SUBMITTER: Hall R 

PROVIDER: S-EPMC7291376 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature