Simulations of anionic lipid membranes: development of interaction-specific ion parameters and validation using NMR data.

Overbinding of ions to lipid head groups is a potentially serious artifact in simulations of charged lipid bilayers. In this study, the Lennard-Jones radii in the CHARMM force field for interactions of Na(+) and lipid oxygen atoms of carboxyl, phosphate, and ester groups were revised to match osmotic pressure data on sodium acetate and electrophoresis data on palmitoyloleoyl phosphatidylcholine (POPC) vesicles. The new parameters were then validated by successfully reproducing previously published experimental NMR deuterium order parameters for dimyristoyl phosphatidylglycerol (DMPG) and newly obtained values for palmitoyloleoyl phosphatidylserine (POPS). Although the increases in Lennard-Jones diameters are only 0.02-0.12 Å, they are sufficient to reduce Na+ binding, and thereby increase surface areas per lipid by 5-10% compared with the unmodified parameters.