A top-down and bottom-up combined strategy for parameterization of coarse-grained force fields for phospholipids

Abstract

Coarse-graining (CG) molecular dynamics (MD) simulations are widely used in interpreting experimental observations and predicting assembly morphology as well as collective behaviour but also face the problem of poor accuracy. A main issue is that cross-termed interactions between different CG beads are inadequately parameterized. This work proposes a novel top-down and bottom-up combined strategy to parameterize both self- and cross-termed interactions of zwitterionic phospholipids in water solution based on a piecewise Morse potential describing nonbonded van der Waals interactions. The self-interacting force parameters were optimized by matching experimental density, heat vapourization, and surface tension in a top-down manner, while the cross-termed interactions were optimized by fitting pseudo properties obtained from atomistic simulations in a bottom-up way, including mixing density, intermolecular energy, and radial mixing coefficient. The transferability of the CG force field (FF) was confirmed by reproducing a variety of structural and thermodynamic properties of lipid membranes in both liquid and gel phases. This FF can well depict vesicle self-assembly and vesicle fusion processes. Matching pseudo properties opens a new way to develop CG FF with increased accuracy and transferability.