Vitamin E's Affinity for Polyunsaturated Phospholipids Studied by All-Atom MD Simulations

Abstract

Vitamin E (α-tocopherol) is the principle lipid soluble antioxidant in cell membranes. Its purpose is to protect membrane lipids from oxidative damage. With all-atom (AA) MD simulations we address how affinity to various lipid species optimizes vitamin E's ability to protect polyunsaturated phospholipids that are most vulnerable to oxidation. Umbrella sampling simulations reveal that the binding energy of vitamin E simulations is greater for saturated SM (sphingomyelin) than polyunsaturated PDPC (1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine). Preferential affinity for polyunsaturated phospholipids is not identified. The binding energy is reduced when cholesterol is added, however, suggesting vitamin E, like polyunsaturated phospholipids, is forced out of (raft-like) regions enriched in cholesterol into (non-raft) regions depleted in cholesterol. With large scale, microsecond-long simulations run on the Anton 2 supercomputer we determine where vitamin E prefers to locate in bilayers assembled with pre-formed PDPC and SM/cholesterol domains. The results of these studies will be presented.