Molecular simulations of self-assembled ceramide bilayers: comparison of structural and barrier properties

Structural and transport properties of lipid bilayers consisting of pure ceramides are investigated through molecular dynamics simulations. Two different initial configurations are used: one where the lipids already form a pre-constructed bilayer and one obtained from the self-assemblage of lipids randomly distributed in an aqueous phase. The latter is created using the MARTINI coarse-grained forcefield followed by back-mapping to atomistic description using the CHARMM forcefield. It is found that the pre-constructed and the self-assembled bilayers have in general comparable structural properties. Nevertheless they exhibit certain differences with respect to the packing and conformation of the aliphatic chains, leading to a different energy barrier that a drug molecule such as ibuprofen must overcome in order to move along the bilayer normal. These results show that the choice of the initial lipids setup for molecular dynamics simulations of a lipid bilayer may have a significant impact on the simulation outcome and thus, the respective calculated structure and transport properties.