Effect of Force Field Parameters on Sodium and Potassium Ion Binding to Dipalmitoyl Phosphatidylcholine Bilayers

The behavior of electrolytes in molecular dynamics simulations of zwitterionic phospholipid bilayers is very sensitive to the force field parameters used. Here, several 200 ns molecular dynamics of simulations of dipalmitoyl phosphotidylcholine (PC) bilayers in 0.2 M sodium or potassium chloride using various common force field parameters for the cations are presented. All employed parameter sets give a larger number of Na(+) ions than K(+) ions that bind to the lipid heads, but depending on the parameter choice quite different results are seen. A wide range of coordination numbers for the Na(+) and K(+) ions is also observed. These findings have been analyzed and compared to published experimental data. Some simulations produce aggregates of potassium chloride, indicating (in accordance with published simulations) that these force fields do not reproduce the delicate balance between salt and solvated ions. The differences between the force fields can be characterized by one single parameter, the electrostatic radius of the ion, which is correlated to σMO (M represents Na(+)/K(+)), the Lennard-Jones radius. When this parameter exceeds a certain threshold, binding to the lipid heads is no longer observed. One would, however, need more accurate experimental data to judge or rank the different force fields precisely. Still, reasons for the poor performance of some of the parameter sets are clearly demonstrated, and a quality control procedure is provided.