The ELBA Force Field for Coarse-Grain Modeling of Lipid Membranes

Abstract

A new coarse-grain model for molecular dynamics simulation of lipid membranes is presented. Following a simple and conventional approach, lipid molecules are modeled by spherical sites, each representing a group of several atoms. In contrast to common coarse-grain methods, two original (interdependent) features are here adopted. First, the main electrostatics are modeled explicitly by charges and dipoles, which interact realistically through a relative dielectric constant of unity (). Second, water molecules are represented individually through a new parametrization of the simple Stockmayer potential for polar fluids; each water molecule is therefore described by a single spherical site embedded with a point dipole. The force field is shown to accurately reproduce the main physical properties of single-species phospholipid bilayers comprising dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylethanolamine (DOPE) in the liquid crystal phase, as well as distearoylphosphatidylcholine (DSPC) in the liquid crystal and gel phases. Insights are presented into fundamental properties and phenomena that can be difficult or impossible to study with alternative computational or experimental methods. For example, we investigate the internal pressure distribution, dipole potential, lipid diffusion, and spontaneous self-assembly. Simulations lasting up to 1.5 microseconds were conducted for systems of different sizes (128, 512 and 1058 lipids); this also allowed us to identify size-dependent artifacts that are expected to affect membrane simulations in general. Future extensions and applications are discussed, particularly in relation to the methodology's inherent multiscale capabilities.

Comparative assessment of the ELBA coarse-grained model for water

“…In the ELBA model [12,13], a water molecule is described by a single interaction site, comprising a Lennard-Jones sphere embedded with a point dipole. The total potential energy U ij of an interacting pair of sites i, j is the point dipole term.…”

“…To calculate the z-dependent electrical profiles from simulation, the relevant quantities were evaluated by summing and averaging over discrete slabs parallel to the xyplane [12,13,37]; the thickness of each slab was 0.1 Å .…”

“…The results obtained with ELBA are in overall good agreement with the experimental data, and in better agreement compared to some of the atomistic models. For density and diffusion, the high accuracy of ELBA is achieved through explicit fitting to experiment [12]. On the other hand, potential energy and heat of vaporisation were not targeted in the parametrisation; hence their good agreement with the experimental values is noteworthy.…”

“…In this work, we consider the coarse-grained ELBA model for water, originally developed as a solvent for lipid membranes [12,13], and we investigate its ability to reproduce fundamental properties of bulk liquid water and the water-vapour interface. In general, coarse-grained modelling involves using single particles to represent collections of nearby atoms, with the aim of reducing the computational cost while retaining fundamental physical features [14][15][16].…”

Nonuniqueness of local stress of three-body potentials in molecular simulations

“…Two opposing forces, interfacial tension and steric repulsion, produce the inhomogeneous stress inside the bilayers [19]. This inhomogeneity is a key property of the bilayers because it determines the area per lipid molecule [19], spontaneous curvature [20][21][22][23][24], Gaussian curvature modulus [21][22][23][24][25][26][27][28], and function of the mechanosensitive channel [29,30]. Since the stress profile cannot be obtained experimentally [31,32], estimation using molecular simulations is important.…”