Structures, dynamics, and water permeation free energy across bilayers of Lipid A and its analog studied with molecular dynamics simulation.

Fundamental studies of the supramolecular layer structures, dynamics and water permeation free energy of hexa-acyl-chain Lipid A and its analogue of tetra-acyl chains would be useful for polymer membranes design for endotoxin removal in water treatment, drug delivery and other biotechnologies. In this work, we studied their supramolecular bilayer by using molecular dynamics simulations and efficient free energy computations. Our simulation accuracy was verified by the agreement between the bilayer structural properties (structure factor, bilayer thickness, and the area per lipid) and lateral diffusion coefficient in our simulation and experimental measurements. More importantly, our simulation for the first time illustrated hexagonal compact packing of the hydrocarbon acyl chains within a leaflet of Lipid A membrane (at 298 K and water content of 40 wt %), which is consistent with experiments. In contrast, Lipid A analogue is found with less ordered ripple structures at the same condition. Our study also demonstrated slower dynamics and larger and broader free energy barrier (∼23 kJ/mol) for water permeation for Lipid A, compared with that of Lipid A analogue. Moreover, the analysis of dynamics showed that highly hydrated hydrophilic diglucosamine backbone is structurally stable, whereas the interdigitated hydrophobic acyl chain tails inside the membrane with faster dynamics screen the aqueous environment from the lipid interior and also reinforce the membrane's structural stability.