Identification of a Novel Class of BRD4 Inhibitors by Computational Screening and Binding Simulations.

ABSTRACT: Computational screening is a method to prioritize small-molecule compounds based on the structural and biochemical attributes built from ligand and target information. Previously, we have developed a scalable virtual screening workflow to identify novel multitarget kinase/bromodomain inhibitors. In the current study, we identified several novel N-[3-(2-oxo-pyrrolidinyl)phenyl]-benzenesulfonamide derivatives that scored highly in our ensemble docking protocol. We quantified the binding affinity of these compounds for BRD4(BD1) biochemically and generated cocrystal structures, which were deposited in the Protein Data Bank. As the docking poses obtained in the virtual screening pipeline did not align with the experimental cocrystal structures, we evaluated the predictions of their prec

SUBMITTER: Allen BK 

PROVIDER: S-EPMC5579542 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature