Hybrid In Silico and TR-FRET-Guided Discovery of Novel BCL-2 Inhibitors.

ABSTRACT: B-Cell lymphoma 2 (BCL-2) regulates cell death in humans. In this study, combined multiscale in silico approaches and in vitro studies were employed. A small-molecule library that includes more than 210 000 compounds was used. The predicted therapeutic activity value (TAV) of the compounds in this library was computed with the binary cancer quantitative structure-activity relationships (QSAR) model. The molecules with a high calculated TAV were used in 26 individual toxicity QSAR models. As a result of this screening protocol, 288 nontoxic molecules with high predicted TAV were identified. These selected hits were then screened against the BCL-2 target protein using hybrid docking and molecular dynamics (MD) simulations. The interaction energies of identified compounds were c

SUBMITTER: Sahin K 

PROVIDER: S-EPMC8204324 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature