An improved empirical potential energy function for molecular simulations of phospholipids

Improvements in the CHARMM all-atom force field for atomic-level molecular simulations of lipids are reported. Substantial adjustments have been made to the Lennard-Jones (LJ) hydrocarbon and torsional parameters and to the p artial atomic charges and torsional parameters of the phosphate moiety. The se changes were motivated by a combination of unexpected simulation results and recent high-level ab initio quantum mechanical calculations. The param eter optimization procedure is described, and the resulting energy function validated by an 11 ns molecular dynamics simulation of a hydrated phosphol ipid bilayer. Of note is the influence of the hydrocarbon LJ parameters on the conformational properties of the aliphatic tails, emphasizing the impor tance of obtaining the proper balance between the bonded and nonbonded port ions of the force field. Compatibility with the CHARMM all-atom parameter s ets for proteins and nucleic acids has been maintained such that high quali ty simulations of biologically interesting membranes are possible. The comp lete force field is included as Supporting Information and is available fro m www.pharmacy.umaryland.edu/similar to alex.