Computational study of paroxetine-like inhibitors reveals new molecular insight to inhibit GRK2 with selectivity over ROCK1.

ABSTRACT: The G-protein coupled receptor kinase 2 (GRK2) regulates the desensitization of beta-adrenergic receptors (β-AR), and its overexpression has been implicated in heart failure. Hence, the inhibition of GRK2 is considered to be an important drug target for the treatment of heart failure. Due to the high sequence similarity of GRK2 with the A, G, and C family (AGC family) of kinases, the inhibition of GRK2 also leads to the inhibition of AGC kinases such as Rho-associated coiled-coil kinase 1 (ROCK1). Therefore, unraveling the mechanisms to selectively inhibit GRK2 poses an important challenge. We have performed molecular docking, three dimensional quantitative structure activity relationship (3D-QSAR), molecular dynamics (MD) simulation, and free energy calculations techniques on a series of

SUBMITTER: Keretsu S 

PROVIDER: S-EPMC6736929 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature