Molecular Simulation of the DPPE Lipid Bilayer Gel Phase: Coupling between Molecular Packing Order and Tail Tilt Angle.

The structural properties and thermal stability of dipalmitoylphosphatidylethanolamine (DPPE) in the ordered gel phase have been studied by molecular dynamics simulation using two force fields: the Berger united-atom model and the CHARMM C36 atomistic model. As is widely known, structural features are sensitive to the initial preparation of the gel phase structure, as some degrees of freedom are slow to equilibrate on the simulation time scale of hundreds of nanoseconds. In particular, we find that the degree of alignment of the lipids' glycerol backbones, which join the two hydrocarbon tails of each molecule, strongly affects the tilt angle of the tails in the resulting structures.

Atomistic simulation of cholesterol effects on miscibility of saturated and unsaturated phospholipids: implications for liquid-ordered/liquid-disordered phase coexistence.

Mixed MD/MC simulation at fixed difference in chemical potential (Δμ) between two lipid types provides a computational indicator of the relative affinities of the two lipids for different environments. Applying this technique to ternary DPPC/DOPC/cholesterol bilayers yields a DPPC/DOPC ratio that increases with increasing cholesterol content at fixed Δμ, consistent with the known enrichment of DPPC and cholesterol-rich in liquid-ordered phase domains in the fluid-fluid coexistence region of the ternary phase diagram. Comparison of the cholesterol-dependence of PC compositions at constant Δμ with experimentally measured coexistence tie line end point compositions affords a direct test of the faithfulness of the atomistic model to experimental phase behavior.

Determination of phase transition temperatures for atomistic models of lipids from temperature-dependent stripe domain growth kinetics.

Many lipid bilayers undergo a reversible order-disorder transition between the gel and liquid crystalline (LC) phases at a main phase transition temperature T(m) that is an important characteristic property of the lipid. Although T(m) should serve as a useful standard for validation and calibration of simulation models of lipid bilayers, its evaluation within simulations is difficult due to the slow kinetics of the gel-LC transition, especially near T(m). A stripe growth strategy for calculating T(m), which aims to bypass the slowest steps in this transition, has been applied to dipalmitoylphosphatidylcholine and distearoylphosphatidylcholine bilayers represented with a commonly used united-atom force field.

Atomistic simulations of mixed-lipid bilayers in gel and fluid phases.

The slow rate of diffusive mixing poses a challenge for molecular dynamics (MD) simulation studies of mixed-lipid bilayers. A mixed Monte Carlo-molecular dynamics (MC-MD) approach, which uses mutation moves to swap lipid types throughout the system within the semi-grand canonical ensemble, is here applied to a comparison of binary mixtures in the gel and liquid crystalline phases. The two lipid components modeled, distearoylphosphatidylcholine (DSPC) and dimyristoylphosphatidylcholine (DMPC), differ by four carbons in the lengths of their acyl tails and are investigated here at full hydration at a temperature (313 K) between their transition temperatures, where coexistence between a DSPC-rich gel phase and a DMPC-rich liquid crystalline phase is expected.