Molecular dynamics simulation of a bilayer of 200 lipids in the gel and in the liquid-crystal phases

We have constructed and simulated a membrane-water system which consists of 200 molecules of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine forming a rectangular patch of a bilayer and of 5483 water molecules covering the head groups on each side of the bilayer. The total number of atoms is approximately 27 000. The lateral dimensions of the bilayer are 85 Å × 100 Å, and the distance between the bilayer surfaces as given by the average phosphorus to phosphorus distance is 35 Å. The thickness of each water layer is up to 15 Å. In all, we simulated 263 ps of the dynamics of the system. To prevent system disintegration, atoms within 5 Å from the surface were harmonically restrained and treated by Langevin dynamics, forming a stochastic boundary. Interior lipids and water molecules were unrestrained. The first 120 ps of the dynamics calculation were used to equilibrate the system and to achieve a low internal pressure. We performed two simulations for analysis: simulation I of the system that resulted from the equilibration; simulation II of the system after an increase of the area per head group from 46 to 70 Ų. The decrease of the lateral lipid density was achieved by scaling the atomic x-, y-, and z-coordinates independently, leaving the volume of the system constant. For both simulations I and II, we determined the internal pressure, the lipid self-diffusion coefficients, the order parameter profile, the distribution of molecular groups, and other properties. The parameters extracted from simulation II are in good agreement with observations on bilayers in the liquid-crystal phase. We provide evidence that the bilayer of simulation I corresponds to the gel phase. The membrane structures resulting from this work can be used for molecular dynamics investigations of membrane proteins, e.g., for the study of lipid-protein interactions or for the equilibration of structural models.