Characterizing the binding interactions between P-glycoprotein and eight known cardiovascular transport substrates.

ABSTRACT: The multidrug efflux pump P-glycoprotein (Pgp) is upregulated in cardiomyocytes following chronic ischemia from infarction and hypoxia caused by sleep apnea. This report summarizes the molecular dynamic studies performed on eight cardiovascular drugs to determine their corresponding binding sites on mouse Pgp. Selected Pgp transport ligands include: Amiodarone, Bepridil, Diltiazem, Dipyridamole, Nicardipine, Nifedipine, Propranolol, and Quinidine. Extensive molecular dynamic equilibration simulations were performed to determine drug docking interactions. Distinct binding sites were not observed, but rather a binding belt was seen with multiple residues playing a role in each studied drug's stable docking. Three key drug-protein interactions were identified: hydrogen bonding, hydrophobic pa

SUBMITTER: Jagodinsky JC 

PROVIDER: S-EPMC4324688 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature