Interaction of drugs amlodipine and paroxetine with the metabolizing enzyme CYP2B4: a molecular dynamics simulation study

The interactions of the drugs amlodipine and paroxetine, which are prescribed respectively for treatment of hypertension and depression, with the metabolizing enzyme cytochrome CYP2B4 as the drug target, have been studied by molecular dynamics (MD) simulation. Poly ethylene glycol was used to control the drugs’ interactions with each other and with the target CYP2B4. Thirteen simulation systems were carefully designed, and the results obtained from MD simulations indicated that amlodipine in the PEGylated form prescribed with paroxetine in the nonPEGylated form promotes higher cytochrome stability and causes fewer fluctuations as the drugs approach the target CYP2B4 and interact with it. The simulation results led us to hypothesize that the combination of the drugs with a specific drug ratio, as proposed in this work, manifests more effective diffusivity and less instability while metabolizing with enzyme CYP2B4. Also, the active residues in the CYP2B4 enzyme that interact with the drugs were determined by MD simulation, which were consistent with the reported experimental results. Graphical Abstract Efficient drug-enzyme interactions, as a result of PEGylation.