Phase-transition properties of glycerol-monopalmitate lipid bilayers investigated by molecular dynamics simulation: influence of the system size and force-field parameters

Phase-transition properties of glycerol-1-monopalmitate (GMP) bilayers are investigated using explicit-solvent molecular dynamics (MD) simulations, initiated from structures appropriate for the gel (GL) or liquid crystal (LC) phases, and carried out at different hydration levels and temperatures. Building up on a previous study and based on 600 ns simulations, the influence of the system size and of the force field on the equilibrium thermodynamic and dynamic parameters of the bilayers in the GL and LC phases, as well as on the temperature T_m and properties of the GL ? LC phase transition, are analysed. Qualitatively speaking, the results agree with the available experimental data for the area per lipid in the two phases and for the phase-transition temperatures at the three hydration levels irrespective of the selected model parameters. They also suggest that the total number of hydrogen bonds formed between a lipid headgroup and its environment is essentially constant, amounting to about four in both the LC and the GL phases. Quantitatively speaking, the dependence of T_m on the hydration level is found to be non-systematic across the different combinations of model parameters. This results in part from a sensitivity of the results on the system size and force-field parameters but also from the limited accuracy of the bracketing approach employed here to estimate T_m. Finally, a simple kinetic model is proposed to account for the timescales of the transitions. This model involves enthalpy and entropy increases of about 26 kJ mol^? 1 and 83 J mol^? 1 K^? 1 per lipid, upon going from the GL to the LC phase. The transition state is associated with activation parameters corresponding to 13% and 11%, respectively, of these values along the GL → LC transition, resulting in an activation free energy of about 0.3 kJ mol^? 1 per lipid at T_m.