(261b) Biomolecular Simulations With the Transferable Potentials for Phase Equilibria: Extension to Phosphlipids

The Transferable Potentials for Phase Equilibria (TraPPE) is extended to zwitterionic and charged lipids including phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylglycerol (PG).   The performance of the force field is validated through isothermal-isobaric ensemble (NPT) molecular dynamics simulations of hydrated lipid bilayers performed with the aforementioned head groups combined with saturated and unsaturated alkyl tails containing 12 – 18 carbon atoms.  To highlight the transferable nature of the TraPPE force field, Lennard-Jones parameters developed for the prediction of vapor-liquid equilibria for low molecular weight organic molecules are used without modification.  Partial charges are determined from a CHELPG analysis of HF/6-31+G(d,p) ab initio calculations, while torsional parameters are refit to match the rotational barriers predicted by the CHARMM C36 lipid force field and MP2/6-31G(d) ab initio calculations.  The effects of water model (TIP3P [1] vs. SPC/E [2]) and sodium ion parameter (Roux [3] vs. Aqvist [4]) on the performance of the lipid force field are determined.  The predictions of the TraPPE force field for the area per lipid, bilayer thickness and volume per lipid are within 1-5% of experimental values.  Key structural properties of the bilayer, such as order parameter splitting in the sn-2 chain and x-ray form factors are found to be in close agreement with experimental data.  Overall, these results highlight the broad transferability of the Transferable Potentials for Phase Equilibria, which was originally developed for the prediction of vapor-liquid coexistence, to the simulation of complex biological systems. 

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