Abstract: Molecular dynamics simulations of α-tocopherol in a number of saturated phospholipid bilayers were performed at 280, 310, and 350 K. The phospholipids contained either short acyl tails, i.e., dimyristoylphosphatidylcholine and dimyristoylphosphatidylethanolamine or long acyl tails, namely distearoylphosphatidylcholine and distearoylphosphatidylethanolamine. The preferential position, hydrogen bonding, orientation, and dynamic properties of α-tocopherol in the bilayers were examined in detail and several conclusions were made. First, the hydroxyl group of α-tocopherol generally remains beneath the interfacial region of the lipid bilayers and it shifts toward the bilayer mid-plane with an increase in temperature. At 350 K it flip-flops between the upper and lower leaflets in the four lipid bilayers. Second, α-tocopherol mainly forms hydrogen bonds with the carbonyl ester oxygen in the lipid head groups and hardly forms hydrogen bonds with the amino groups in the phosphatidylethanolamine (PE) bilayers. Hydrogen bonding with PEs is more stable than hydrogen bonding with phosphatidylcholines (PCs) at low temperatures. Third, α-tocopherol's head group has fluctuating tilt angles relative to the normal of the lipid bilayers and the tail has many different conformations. Fourth, the lateral diffusion rate of α-tocopherol is comparable to that of phospholipid molecules at low temperature and it diffuses much faster than lipids at 350 K. The diffusion rate in the direction perpendicular to the membrane surface is much slower than the lateral diffusion rate.

Key words: Vitamin E, Phospholipid, Orientation, Flip-flop, Diffusion, Hydrogen-bond