Drude Polarizable Force Field for Molecular Dynamics Simulations of Saturated and Unsaturated Zwitterionic Lipids.

Abstract

Additive force fields are designed to account for induced electronic polarization in a mean-field average way, using effective empirical fixed charges. The limitation of this approximation is cause for serious concerns, particularly in the case of lipid membranes, where the molecular environment undergoes dramatic variations over microscopic length scales. A polarizable force field based on the classical Drude oscillator offers a practical and computationally efficient framework for an improved representation of electrostatic interactions in molecular simulations. Building on the first-generation Drude polarizable force field for the dipalmitoylphosphatidylcholine 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) molecule, the present effort was undertaken to improve this initial model and expand the force field to a wider range of phospholipid molecules. New lipids parametrized include dimyristoylphosphatidylcholine (DMPC), dilauroylphosphatidylcholine (DLPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), dipalmitoylphosphatidylethanolamine (DPPE), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). The iterative optimization protocol employed in this effort led to lipid models that achieve a good balance between reproducing quantum mechanical data on model compound representative of phospholipids and reproducing a range of experimental condensed phase properties of bilayers. A parametrization strategy based on a restrained ensemble-maximum entropy methodology was used to help accurately match the experimental NMR order parameters in the polar headgroup region. All the parameters were developed to be compatible with the remainder of the Drude polarizable force field, which includes water, ions, proteins, DNA, and selected carbohydrates.