Leng, XiaolingZhu, FangqiangWassall, Stephen R.2018-10-042018-10-042018Leng, X., Zhu, F., & Wassall, S. R. (2018). Vitamin E Has Reduced Affinity for a Polyunsaturated Phospholipid: An Umbrella Sampling MD Simulations Study. The Journal of Physical Chemistry B, 122 (35), pp 8351–8358. https://doi.org/10.1021/acs.jpcb.8b05016https://hdl.handle.net/1805/17442Vitamin E is an essential micronutrient. The primary function of this lipid-soluble antioxidant is to protect membrane phospholipids from oxidation. Whether vitamin E preferentially interacts with polyunsaturated phospholipids to optimize protection of the lipid species most vulnerable to oxidative attack has been an unanswered question for a long time. In this work, we compared the binding of α-tocopherol (αtoc), the form of vitamin E retained by the human body, in bilayers composed of polyunsaturated 1-stearoyl-2-docosahexaenoylphosphatidylcholine (SDPC, 18:0-22:6PC) and, as a control, monounsaturated 1-stearoyl-2-oleoylphosphatidylcholine (SOPC, 18:0-18:1PC) by umbrella sampling molecular dynamics simulations. From the potential of mean force as a function depth within the bilayer, we find that the binding energy of αtoc is less in SDPC (ΔGbind = 16.7 ± 0.3 kcal/mol) than that in SOPC (ΔGbind = 18.3 ± 0.4 kcal/mol). The lower value in SDPC is ascribed to the high disorder of polyunsaturated fatty acids that produces a less tightly packed arrangement. Deformation of the bilayer is observed during desorption, indicating that phosphatidylcholine (PC)–PC and αtoc–PC interactions contribute to the binding energy. Our results do not support the proposal that vitamin E interacts more favorably with polyunsaturated phospholipids.enPublisher Policyvitamin Epolyunsaturated phospholipidsumbrella sampling molecular dynamics simulationsArticle