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. The strategy consists of initial preparation of a bilayer containing gel and LC domains arranged as parallel stripes, observation of the direction and rate of domain growth over a range of temperatures, and fitting rates to an Arrhenius-like equation for their temperature dependence that crosses zero at T(m). Calculated T(m)'s for both lipids are 5-6 degrees lower than their experimental values, in much closer agreement with experiment than suggested by recent simulations that simulate heating and cooling of bilayer patches. The stripe growth method also yields rates of phase front propagation that are in order-of-magnitude agreement with experimental estimates, as well as insight into glycerol backbone disordering at the LC-gel interface.

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. DPPC/DOPC ratios show little or no dependence on cholesterol content at or below 16% cholesterol in the DOPC-rich region of the composition diagram, indicating cooperativity in the favorable interaction between DPPC and cholesterol. The relative affinity of DPPC and DOPC for high cholesterol bilayer environments in simulations is explicitly shown to depend on the degree of cholesterol alignment with the bilayer normal, suggesting that a source of the cooperativity is the composition dependence of cholesterol tilt angle distributions.