Implicit solvent systematic coarse-graining of dioleoylphosphatidylethanolamine lipids: From the inverted hexagonal...

Lamellar and hexagonal lipid structures are of particular importance in the biological processes such as membrane fusion and budding. Atomistic simulations of formation of these phases and transitions between them are computationally prohibitive, hence development of coarse-grained models is an important part of the methodological development in this area. Here we apply systematic bottom-up coarse-graining to model different phase structures formed by 1,2-dioleoylphosphatidylethanolamine (DOPE) lipid molecules. We started from atomistic simulations of DOPE lipids in water carried out at two different water/lipid molar ratio corresponding to the lamellar Lα and inverted hexagonal HII structures at low and high lipid concentrations respectively. The atomistic trajectories were mapped to coarse-grained trajectories, in which each lipid was represented by 14 coarse-grained sites. Then the inverse Monte Carlo method was used to compute the effective coarse-grained potentials which for the coarse-grain model reproduce the same structural properties as the atomistic simulations. The potentials derived from the low concentration atomistic simulation were only able to form a bilayer structure, while both Lα and HII lipid phases were formed in simulations with potentials obtained at high concentration. The typical atomistic configurations of lipids at high concentration combine fragments of both lamellar and non-lamellar structures, that is reflected in the extracted coarse-grained potentials which become transferable and can form a wide range of structures including the inverted hexagonal, bilayer, tubule, vesicle and micellar structures.