(686e) Development of the TraPPE Force Field for Phospholipids

The transferable potentials for phase equilibria (TraPPE) force field has been widely used for the simulation of vapor-liquid coexistence and condensed phase structure for small organic molecules [1], but to date has seen little use in the simulation of biological systems. An integral component of biological machinery is the bio-membrane (primarily composed of phospholipids and certain embedded proteins) which provides a defined boundary to cell cytoplasm and to smaller systems like liposome and vesicles. Study of bilayer interactions with various proteins (either membrane free or bound) such as signaling proteins, antimicrobials or synthetic peptides is an area of significant research interest [2-4]. In addition to in vitro analysis, molecular dynamics simulation techniques have become popular over the last few years for research and the analysis of biological systems at the atomic level. At the heart of molecular simulations is the force field which plays a major role in determining the accuracy of a simulation and is specific for a particular class of molecules. Several force fields have been developed for lipid simulations over the past decade such as all-atom based CHARMM [5] and united-atom based Berger [6] and GROMOS [7]. In this work, the TraPPE force field is extended to lipid molecules and has been developed for neutral charged phospholipids including dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylcholine (DMPC) and dilauroylphosphatidylcholine (DLPC). Previously developed TraPPE united atom parameters for Lennard-Jones interactions have been used without modification. Partial charges were developed using CHELPG analysis of HF/6-31G(d,p) calculations. The force field is validated by performing NPT molecular dynamics simulations on homogenous bilayer systems followed by analysis of structural properties of the bilayer such as area per lipid, volume per lipid, bilayer thickness, order parameters and comparison of the same with the experimental values. For all the considered lipids, area per lipid and bilayer thickness values lie within 2% range of experiment. Electron density, volume per lipid and order parameters are also found to be in close agreement with experimental data. Overall, these results highlight the transferable nature of the TraPPE force field. References 1. Sokkalingam, N. et al. J. Phys. Chem. B. 113, 10292 (2009) 2. Gorfe, A.A. et al. J. Am. Chem. Soc. 129, (40), 12280 (2007) 3. La Rocca, P. et al. Biochim. Biophys. Acta - Biomembr. 1462, 185 (1999) 4. Ishiguro, R. et al. Biochemistry 35, (15), 4976 (1996) 5. Feller, S.E. et al. J. Phys. Chem. B. 104, 7510 (2000) 6. Berger, O. et al. Biophys. J. 72, 2002 (1997) 7. Chandrasekhar, I. et al. Eur. Biophys. J. 32, (1), 67 (2003)