An analysis of the dipalmitoylphosphatidylcholine bilayer gel phases predicted with molecular dynamics simulations using force fields from the GROMOS family

Abstract

Dipalmitoylphosphatidylcholine is a phospholipid of major importance for biological systems. Molecular dynamics simulation investigations of this lipid focused on their behavior at human body temperature (≈ 37 °C or 310 K). For some applications, however, it is necessary to study its properties at room temperature (≈ 25 °C or 298 K). A small difference in temperature at this range is responsible for a phase transition in the lipid bilayer. Therefore, molecular dynamics simulations are carried out applying four different force fields from the GROMOS family to compare the less ordered phase (liquid-crystalline phase) with a more ordered phase (gel phase) of the hydrated bilayer of dipalmitoylphosphatidylcholine formed at 323 K and 298 K, respectively. The analysis of the bilayer structural quantities is used to evaluate order and packing at the two temperatures. The area per lipid and deuterium order parameter results are in agreement with simulation results from the literature and are also compared with experimental data. These parameters, however, do not provide a clear picture of the low-temperature gel phase present in the simulations using the force fields from the GROMOS family. To address this, a strategy for computing the lipid phase nematic order parameter is proposed, and a reference gel phase is simulated using the CHARMM36 force field for comparison. The results are consistent with other structural quantities but reveal a level of order that is below the expected for an ordered gel phase for the GROMOS force fields. Visual inspection of the simulation trajectories suggests the presence of a ripple phase. Overall, the GROMOS 54A8 provides the best performance among the tested GROMOS force fields for both investigated temperatures, even lacking a proper representation of the ordered gel phase.