Understanding the P-Loop Conformation in the Determination of Inhibitor Selectivity Toward the Hepatocellular Carcinoma-Associated Dark Kinase STK17B.

ABSTRACT: As a member of the death-associated protein kinase family of serine/threonine kinases, the STK17B has been associated with diverse diseases such as hepatocellular carcinoma. However, the conformational dynamics of the phosphate-binding loop (P-loop) in the determination of inhibitor selectivity profile to the STK17B are less understood. Here, a multi-microsecond length molecular dynamics (MD) simulation of STK17B in the three different states (ligand-free, ADP-bound, and ligand-bound states) was carried out to uncover the conformational plasticity of the P-loop. Together with the analyses of principal component analysis, cross-correlation and generalized correlation motions, secondary structural analysis, and community network analysis, the conformational dynamics of the P-loop in the diff

SUBMITTER: Liu C 

PROVIDER: S-EPMC9127184 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature