Diffusion of 1,2-dimethoxyethane and 1,2-dimethoxypropane through phosphatidycholine bilayers: A molecular dynamics study

In this paper, a theoretical study of 1,2-dimethoxyethane (DME) and 1,2-dimethoxypropane (DMP) at water/n-heptane and 1,2-dimyristoyl-sn-glycero-3- phospatidycholine (DMPC) lipid bilayer/water interfaces using the umbrella sampling method is reported. Recently proposed GROMOS96/OPLS compatible models for DME and DMP have been used for the simulation studies. The percolation free energy barrier of one DME and DMP molecule from water to n-heptane phase calculated using the umbrella sampling method turned out to be equal to ∼18.5 kJ/mol and ∼6 kJ/mol, respectively. In the case of the DMPC lipid bilayer, overall free energy barriers of ∼20 kJ/mol and ∼12 kJ/mol were obtained for DME and DMP, respectively. The spontaneous diffusion of DME and DMP in the lipid bilayer has also been investigated using unconstrained molecular dynamics simulations at the water/DMPC interface and inside the lipid bilayer. As expected from the estimated percolation barriers, simulation results show that DME, contrary to DMP, spontaneously diffuse into the aqueous solution from the lipid interior. In addition, simulations with multiple DME or DMP molecules at the interface show spontaneous diffusion within 50 ns inside the DMPC layer only for DMP. © 2012 American Chemical Society