Modifying the CHARMM36 Lipid Force Field for LJ-PME Simulations

Abstract

Long-range Lennard-Jones (LJ) interactions were historically excluded from energy calculations in Molecular Dynamics (MD) simulations due to high computational cost. However, these interactions have a significant impact on the properties of nonpolar systems. The LJ particle-mesh Ewald (LJ-PME) method offers a solution to this problem and retains good efficiency. Here we introduce a modification to the additive all-atom CHARMM lipid force field (FF) which makes it compatible with the LJ-PME method. The last generation of the CHARMM36 (C36) lipid FF is suitable for NPT simulations of lipid bilayer systems using the PME method for the nonbonded interactions but systematically yields lower values of surface area per lipid compared to experimental estimates when the long-range LJ interactions are included. Here we develop an automated workflow to optimize the parameters of the nonbonded interactions (partial atomic charges and Lennard-Jones parameters). 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) is used as the prototype and various structural properties (surface area per lipid, NMR deuterium order parameters, radial distribution functions of water for selected atoms) are used as targets. In each optimization step, free energy perturbation theory is used to estimate the properties from trajectories generated by the optimal parameters in the previous step. QM calculations of partial atomic charges are also used to guide the optimization. The parametrization improves the above-mentioned properties significantly with small changes to the C36 lipid FF and allows MD simulations of lipid systems to use the LJ-PME method.