Capturing Membrane Phase Separation by Dual Resolution Molecular Dynamics Simulations

Abstract

Understanding the lateral organization in plasma membranes remains an open problem and is of great interest to many researchers. Model membranes consisting of coexisting domains are commonly used as simplified models of plasma membranes. The coarse-grained (CG) Martini force field has successfully captured spontaneous separation of ternary membranes into a liquid-disordered and a liquid-ordered domain. With all-atom (AA) models, however, phase separation is much harder to achieve due to the slow underlying dynamics. To remedy this problem, here, we apply the virtual site (VS) hybrid method on a ternary membrane composed of saturated lipids, unsaturated lipids, and cholesterol to investigate the phase separation. The VS scheme couples the two membrane leaflets at CG and AA resolution. We found that the rapid phase separation reached by the CG leaflet can accelerate and guide this process in the AA leaflet.

Understanding nonlinear composition dependency of enantioselectivity in chiral separation using mixed micelle

“…Molecular dynamics simulations (MD) may be an alternative way to quantify the volumes of the binding site at the boundaries of surfactants. The combination of MD and Voronoi tessellation analysis is used for lipids to derive area per molecule, [69] distribution, [70] phase separation behavior, [71], and lipid area fluctuation. [72] MD simulations of the mixed micelles might obtain detailed information, including the value of v12 and K12, but the elaborated simulation that can reproduce the experimental result will require careful parameterization of the forcefield as well as consideration of various configurations of the surfactants and solutes, which is beyond the scope of this paper.…”

Understanding Nonlinear Composition Dependency of Enantioselectivity in Chiral Separation Using Mixed Micelle

“…Molecular dynamics simulations (MD) may be an alternative way to quantify the volumes of the binding site at the boundaries of surfactants. The combination of MD and Voronoi tessellation analysis is used for lipids to derive area per molecule, 66 distribution, 67 phase separation behavior, 68 , and lipid area fluctuation. 61 MD simulations of the mixed micelles might obtain detailed information, including the value of v12 and K12, but the elaborated simulation that can reproduce the experimental result will require careful parameterization of the forcefield as well as consideration of various configurations of the surfactants and solutes, which is beyond the scope of this paper.…”

Lipase-mediated selective hydrolysis of lipid droplets in phase separated-liposomes

“…Phase separation in CGMD was quantified by the (time-averaged) relative fraction of contacts between the DOaG lipid and the DSPC lipid (see Materials and Methods for more details and Figure S14) following a recently developed method. 49 The DOaG parametrization described here was used for all simulations in the remainder of this study. Significantly different: *P ≤ 0.05, **P ≤ 0.01, ***P < 0.001.…”