A charge-modified general amber force field for phospholipids: improved structural properties in the tensionless ensemble

Abstract

Accurately predicting the structural properties of phospholipid with a fully atomistic molecular model is critical for the study of pure phospholipid bilayers, mixed bilayer systems and bilayers containing proteins. The general amber force field (GAFF) has traditionally required the presence of a surface tension parameter to correctly model phospholipid bilayer properties such as area per lipid and order parameters. In this work, the GAFF partial charges for 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphate (POPA), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphochiline (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) were re-parameterised utilising high-level ab initio calculations and the restrained electrostatic potential method. Simulations of pure POPA, POPC and POPG bilayers using the charge-modified GAFF and no applied surface tension are compared with available experimental data, the original GAFF model and the recent Lipid14 variant. The results indicate a significant improvement in the accuracy of the lipid model for reproducing experimental observables without the need for a surface tension parameter. The successful application of modifying the lipid charge distributions represents an alternative to the use of a surface tension parameter within GAFF, and highlights the importance of the partial charge calculations when modelling lipid bilayers.