INTERACTION BETWEEN DIHYDROPYRIDINES AND PHOSPHOLIPID-BILAYERS - A MOLECULAR-DYNAMICS SIMULATION

Interaction of the calcium-channel antagonist dihydropyridines (DHPs), lacidipine and nifedipine, with a phospholipid bilayer was studied us ing 600 ps molecular dynamic simulations. We have constructed a double layer membrane model composed of 42 dimirystoyl-phosphatidylcholine m olecules. The DHP molecules locate at about 7 Angstrom from the centre of the membrane, inducing an asymmetry in the bilayer. While lacidipi ne did not induce significant local perturbations as judged by the gau che-trans isomerisation rate, nifedipine significantly decreased this rate, probably by producing a local rigidity of the membrane in the vi cinity of the DHP.