Binding Selectivity of Inhibitors toward Bromodomains BAZ2A and BAZ2B Uncovered by Multiple Short Molecular Dynamics Simulations and MM-GBSA Calculations.

ABSTRACT: Two Bromodomain-Containing proteins BAZ2A and BAZ2B are responsible for remodeling chromatin and regulating noncoding RNAs. As for our current studies, integration of multiple short molecular dynamics simulations (MSMDSs) with molecular mechanics generalized Born surface area (MM-GBSA) method is adopted for insights into binding selectivity of three small molecules D8Q, D9T and UO1 to BAZ2A against BAZ2B. The calculations of MM-GBSA unveil that selectivity of inhibitors toward BAZ2A and BAZ2B highly depends on the enthalpy changes and the details uncover that D8Q has better selectivity toward BAZ2A than BAZ2B, D9T more favorably bind to BAZ2B than BAZ2A, and UO1 does not show obvious selectivity toward these two proteins. The analysis of interaction network between residues and inhibitors

SUBMITTER: Wang L 

PROVIDER: S-EPMC8154142 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature