LAUSR

Alpha-tocopherol (αtoc) is the active form of vitamin E that is retained in the human body. It is a lipid-soluble antioxidant, which protects polyunsaturated fatty acids (PUFA) by terminating a chain of chemical reactions that follow free radical attack. Due to the low global concentration of αtoc in the plasma membrane, we have proposed that αtoc preferentially interacts with the PUFA-containing lipids to optimize its local concentration. Here we tested this hypothesis by calculating the binding energy between αtoc and two different phospholipids. 1-stearoyl-2-docosahexaenoylphosphatidylcholine (SDPC, 18:0-22:6PC) was used to represent a PUFA-containing lipid, while 1-stearoyl-2-oleoylphosphatidylcholine (SOPC, 18:0-18:1PC) was used as a monounsaturated control. Umbrella sampling molecular dynamics (USMD) simulations of αtoc in bilayers composed of these lipids were performed with 45 windows separated by 1 A and arranged from the center of bilayer all the way to the bulk water to calculate the free energy as a function of αtoc's location. The results show slightly less binding energy between αtoc and SDPC, which we ascribe to a more loosely packed arrangement of lipids in the PUFA-containing membrane. NMR experiments measuring the affinity of αtoc for SDPC and SOPC are currently ongoing in support of the simulations.