Computer Simulation of Lipids and broadening software choices for the Coarse-Grained Martini Force Field

Abstract

Computer simulation is a powerful approach to study biological membranes. Biophysical properties of lipid molecules and lipid-protein interactions can be studied in silico complementary to experimental methods such as NMR and crystallography. Accurate simulation of membrane systems relies on the force field and the lipid model employed. Atomistic force fields can provide high-resolution molecular details while coarse-grained models provide insight into physiological phenomena at longer timescale and length-scale. Lipid-protein interactions are important in biological functions such as stabilizing membrane proteins and regulating protein activities. We examined the lipid density and cholesterol flip-flop rate in an asymmetric membrane coupled with entities of various shapes embedded in the lipid bilayer. With the generated simulation data, we attempted to improve molecular visualization using new 3D technologies and applying computer graphics to innovate the visualization of 3D molecular data. To expand the choices for coarse-grained simulations, we also extended the compatibility of the coarse-grained Martini force field to OpenMM, another flexible and popular simulation software. Martini version 2 and 3 are now available in OpenMM. Finally, we examined the chain conformation of a model lipid, DPPC, in the Martini simulations and the CHARMM36 model. The coarse-grained acyl chain is compared with a corresponding atomistic ensemble of chain conformations. A given Martini DPPC conformation is shown to represent large numbers of atomistic ensembles. These works contribute to better understand membrane systems in Martini simulations.