Accurate calculation of the absolute free energy of binding for drug molecules.

ABSTRACT: Accurate prediction of binding affinities has been a central goal of computational chemistry for decades, yet remains elusive. Despite good progress, the required accuracy for use in a drug-discovery context has not been consistently achieved for drug-like molecules. Here, we perform absolute free energy calculations based on a thermodynamic cycle for a set of diverse inhibitors binding to bromodomain-containing protein 4 (BRD4) and demonstrate that a mean absolute error of 0.6 kcal mol^-1 can be achieved. We also show a similar level of accuracy (1.0 kcal mol^-1) can be achieved in pseudo prospective approach. Bromodomains are epigenetic mark readers that recognize acetylation motifs and regulate gene transcription, and are currently being investigated as therapeutic t

SUBMITTER: Aldeghi M 

PROVIDER: S-EPMC4700411 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature