Force field dependence of phospholipid headgroup and acyl chain properties: comparative molecular dynamics...

The reliability of molecular simulations largely depends on the quality of the empirical force field parameters. Force fields used in lipid simulations continue to be improved to enhance the agreement with experiments for a number of different properties. In this work, we have carried out molecular dynamics simulations of neat DMPC bilayers using united-atom Berger force field and three versions of all-atom CHARMM force fields. Three different systems consisting of 48, 72, and 96 lipids were studied. Both particle mesh Ewald (PME) and spherical cut-off schemes were used to evaluate the long-range electrostatic interactions. In total, 21 simulations were carried out and analyzed to find out the dependence of lipid properties on force fields, system size, and schemes to calculate long-range interactions. The acyl chain order parameters calculated from Berger and the recent versions of CHARMM simulations have shown generally good agreement with the experimental results. However, both sets of force fields deviate significantly from the experimentally observed P-C dipolar coupling values for the carbon atoms that link the choline and glycerol groups with the phosphate groups. Significant differences are also observed in several headgroup parameters between CHARMM and Berger simulations. Our results demonstrate that when changes were introduced to improve CHARMM force field using PME scheme, all the headgroup parameters have not been reoptimized. The headgroup properties are likely to play a significant role in lipid-lipid, protein-lipid, and ligand-lipid interactions and hence headgroup parameters in phospholipids require refinement for both Berger and CHARMM force fields.