Unveiling Allosteric Regulation and Binding Mechanism of BRD9 through Molecular Dynamics Simulations and Markov Modeling.

ABSTRACT: Bromodomain-containing protein 9 (BRD9) is a key player in chromatin remodeling and gene expression regulation, and it is closely associated with the development of various diseases, including cancers. Recent studies have indicated that inhibition of BRD9 may have potential value in the treatment of certain cancers. Molecular dynamics (MD) simulations, Markov modeling and principal component analysis were performed to investigate the binding mechanisms of allosteric inhibitor POJ and orthosteric inhibitor 82I to BRD9 and its allosteric regulation. Our results indicate that binding of these two types of inhibitors induces significant structural changes in the protein, particularly in the formation and dissolution of α-helical regions. Markov flux analysis reveals notable changes occurring i

SUBMITTER: Wang B 

PROVIDER: S-EPMC11314499 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature