Conformation of nifedipine in hydrated 1,2-di-myristoyl- sn-glycero-3-phosphoryicholine bilayer molecular dynamics simulation

摘要

The conformation of nifedipine, a cardiac and smooth muscle calcium ion channel antagonist is studied in a hydrated bilayer of forty nine 1,2-di-myristoyl-sn-glycero-3-phosphorykho. line (DMPC) molecules using molecular dynamics (MD) simulation technique. The simulation was carried out in conditions of constant number, volume and temperature (NVT) at 310K, which is above the liquid crystalline (L_α) transition temperature of DMPC. The periodic boundary conditions were applied in three-dimensions. Thus the model represented an infinite bilayer. The important geometric parameters characteristic to DMPC and uifedipine molecules were calculated and compared with other theoretical and experimental results pertaining to uifedipine and other related dihydrophyridine (DHP) analogues. Our results suggest that conformational parameters required for antagonist activity are fairly conserved during the interaction of nifedipine with DMPC bilary and bilayer stabilizes the drug conformation in the bioactive form.