Coarse Grained Model for Semiquantitative Lipid Simulations

Abstract

This paper describes the parametrization of a new coarse grained (CG) model for lipid and surfactant systems. Reduction of the number of degrees of freedom together with the use of short range potentials makes it computationally very efficient. Compared to atomistic models a gain of 3-4 orders of magnitude can be achieved. Micrometer length scales or millisecond time scales are therefore within reach. To encourage applications, the model is kept very simple. Only a small number of coarse grained atom types are defined, which interact using a few discrete levels of interaction. Despite the computational speed and the simplistic nature of the model, it proves to be both versatile in its applications and accurate in its predictions. We show that densities of liquid alkanes from decane up to eicosane can be reproduced to within 5%, and the mutual solubilities of alkanes in water and water in alkanes can be reproduced within 0.5 kT of the experimental values. The CG model for dipalmitoylphosphatidylcholine (DPPC) is shown to aggregate spontaneously into a bilayer. Structural properties such as the area per headgroup and the phosphate-phosphate distance match the experimentally measured quantities closely. The same is true for elastic properties such as the bending modulus and the area compressibility, and dynamic properties such as the lipid lateral diffusion coefficient and the water permeation rate. The distribution of the individual lipid components along the bilayer normal is very similar to distributions obtained from atomistic simulations. Phospholipids with different headgroup (ethanolamine) or different tail lengths (lauroyl, stearoyl) or unsaturated tails (oleoyl) can also be modeled with the CG force field. The experimental area per headgroup can be reproduced for most lipids within 0.02 nm 2 . Finally, the CG model is applied to nonbilayer phases. Dodecylphosphocholine (DPC) aggregates into small micelles that are structurally very similar to ones modeled atomistically, and DOPE forms an inverted hexagonal phase with structural parameters in agreement with experimental data.

Coarse Grained Protein−Lipid Model with Application to Lipoprotein Particles

“…The time scales of these processes also agreed with that reported by Marrink et al 30 Marrink's original model was designed for physiological or room temperature systems. 30 Modeled water was reported to melt at 290 K and spontaneously freeze below 240 K. Nevertheless, caution needs to be exercised when applying the present model even at room temperature, since interactions between the water beads are accounted for by a pure LennardJones 12-6 potential, which narrows the liquid range of the CG solvent (i.e., the range of temperatures at which the solvent is in a liquid state might be substantially narrower than the 100 K for real water). For instance, the CG water may eventually begin to freeze in a substantially longer simulation, even at temperatures where it should be liquid.…”

“…For example, we calculated the self-diffusion coefficient of water from our CG simulations to be 4.0 × 10 −5 cm 2 /s, which is two times the experimental value. Marrink et al 30 reported that during their simulations CG diffusion coefficients were 3-6 times larger than those of the equivalent all-atom systems. 30 This implies that CG dynamics speed up relaxation processes 2-6 fold compared with all-atom MD.…”

“…Marrink et al 30 reported that during their simulations CG diffusion coefficients were 3-6 times larger than those of the equivalent all-atom systems. 30 This implies that CG dynamics speed up relaxation processes 2-6 fold compared with all-atom MD. The combination of longer time steps and faster relaxation results in a computational speedup of 50-150 times from an all-atom to a CG description.…”

“…In addition to the reduction in system size, CG models use a combination of short-range electrostatics and minimal number of bead types to further improve computational efficiency. 29,30,31 One of the first CG MD lipid models to successfully show assembly of lipids was developed by Klein and coworkers. 29,32 The developed DMPC CG model was parameterized to mimic structural features resulting from all-atom simulations.…”

A Quantitative Coarse-Grain Model for Lipid Bilayers

“…Other issues affecting the specific CG models developed to date involve the membrane dynamic properties, which are reproduced with some difficulty, and the associated issue in interpreting the simulation time scales. For example, lipid diffusion coefficients have been reported to be 4 40,52 to 100 46 times higher than experimental data; as already pointed out elsewhere, 54 the ad hoc rescaling of the simulation time according to these factors 40,46 is questionable because it assumes that all dynamic events are homogeneous in time scale, whereas, in general, dynamic processes in membrane systems are highly heterogeneous. Another issue concerns the attractive possibility of mixing CG and AL representations in multiscale simulation, where selected parts of the system are described at an atomic level, whereas the surrounding environment is simulated by simplified models.…”