Although the CHARMM36 (C36) lipid force field (FF) has been extended to incorporate various lipids with a high-level of accuracy, the development of the FF was based on cutoffs in the long-range dispersion energies. This works reasonably well with bilayers but fails to represent the properties of lipid assemblies that require long-range dispersion, i.e., lipid monolayers with an air-acyl chain interface. In this presentation, a method to optimize lipid FF parameters in a semi-automated approach is presented to refit the C36 lipid FF to simultaneously reproduce lipid bilayer and monolayer properties. The optimization uses thermodynamic reweighting with regularization to the original C36 FF. Using a reasonably tuned C36 FF as a reference perturbation point, this reweighting approach quickly converges to a set of parameters that match many experimental observables. The ability to quickly obtain an accurate set of parameters for phosphocholine (PC) lipids in the manner of months will allow us to quickly develop a revised C36 with a Lennard Jones particle mesh Ewald (LJ/PME) approach for long-range dispersion. This approach has been used to develop parameters for PC, phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and ether lipids that agree with structural and dynamical properties of bilayers and monolayers. With future optimization on a wider range of lipids, the updated C36/LJ-PME parameters will allow for accurate simulations without the need or dependence on a dispersion cutoff scheme.

Reoptimization of the CHARMM lipid force field for inclusion of long-range dispersion

ACS Spring Meeting 2021

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