Comparison of Intermolecular Interactions of Irreversible and Reversible Inhibitors with Bruton's Tyrosine Kinase via Molecular Dynamics Simulations.

ABSTRACT: Bruton's tyrosine kinase (BTK) is a key protein from the TEC family and is involved in B-cell lymphoma occurrence and development. Targeting BTK is therefore an effective strategy for B-cell lymphoma treatment. Since previous studies on BTK have been limited to structure-function analyses of static protein structures, the dynamics of conformational change of BTK upon inhibitor binding remain unclear. Here, molecular dynamics simulations were conducted to investigate the molecular mechanisms of association and dissociation of a reversible (ARQ531) and irreversible (ibrutinib) small-molecule inhibitor to/from BTK. The results indicated that the BTK kinase domain was found to be locked in an inactive state through local conformational changes in the DFG motif, and P-, A-, and gatekeeper loops

SUBMITTER: Yu X 

PROVIDER: S-EPMC9655453 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature