COMPUTATION OF MIXED PHOSPHATIDYLCHOLINE-CHOLESTEROL BILAYER STRUCTURES BY ENERGY MINIMIZATION

The energetically preferred structures of dimyristoylphosphatidylcholi ne (DMPC)-cholesterol bilayers were determined at a 1:1 mole ratio. Cr ystallographic symmetry operations were used to generate planar bilaye rs of cholesterol and DMPC. Energy minimization was carried out with r espect to bond rotations, rigid body motions, and the two-dimensional lattice constants. The lowest energy structures had a hydrogen bond be tween the cholesterol hydroxyl and the carbonyl oxygen of the sn-2 acy l chain, but the largest contribution to the intermolecular energy was from the nonbonded interactions between the flat a: surface of choles terol and the acyl chains of DMPC. Two modes of packing in the bilayer were found; in structure A (the global minimum), unlike molecules are nearest neighbors, whereas in structure B (second lowest energy) like -like intermolecular interactions predominate. Crystallographic close packing of the molecules in the bilayer was achieved, as judged from t he molecular areas and the bilayer thickness. These energy-minimized s tructures are consistent with the available experimental data on mixed bilayers of lecithin and cholesterol, and may be used as starting poi nts for molecular dynamics or other calculations on bilayers.