Exploring the binding mechanisms of PDE5 with chromeno[2,3-c]pyrrol-9(2H)-one by theoretical approaches.

ABSTRACT: Cyclic nucleotide phosphodiesterase type 5 (PDE5), exclusively specific for the cyclic guanosine monophosphate (cGMP), is an important drug target for the treatment of erectile dysfunction and pulmonary arterial hypertension (PAH). Although many PDE5 inhibitors have been approved, such as sildenafil, vardenafil, tadalafil and so on, extensive studies have reported some side effects, such as vision disturbance and hearing loss as a result of the amino acid sequence and the secondary structural similarity of other PDEs to the catalytic domain of PDE5. In this study, multiple docking strategies, molecular dynamics (MD) simulations, free energy calculations and decomposition were employed to explore the structural determinants of PDE5 with a series of chromeno[2,3-c]pyrrol-9(2H)-

SUBMITTER: Huang X 

PROVIDER: S-EPMC9085377 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature