Department of Mechanical and Industrial Engineering, Louisiana State University, Baton Rouge, LA, 70803, USA.
Center for Computation and Technology, Louisiana State University, Baton Rouge, LA, 70803, USA.
Eur Biophys J. 2021 Sep;50(6):889-903. doi: 10.1007/s00249-021-01548-y. Epub 2021 May 29.
Using molecular dynamics simulations, we investigate the interaction of α-tocopherol (α-toc) with dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylcholine (DMPC), palmitoyloleoylphosphatidylcholine (POPC), and palmitoyloleoylphosphatidylethanolamine (POPE) lipid bilayers. The goal is to develop a better understanding of the positioning and orientation of α-toc inside the bilayers; properties of significant relevance to α-toc anti-oxidant activity. We investigated bilayer systems with 128 lipids in the presence of either single or 14 α-toc molecules. The single α-toc bilayer systems were investigated via biased MD simulations in which the potential of mean force (PMF) and diffusivity were obtained as functions of the distance between α-toc head group and bilayer center. The higher α-toc concentration systems were investigated with unbiased MD simulations. For all four bilayers at both concentrations, the simulations show that the most probable location of the α-toc hydroxyl group is just below the lipid carbonyl group. Overall, the simulation results are in good agreement with existing experimental data except for the DMPC bilayer system for which some experiments predict α-toc to be located closer to bilayer center. The flip-flop frequency calculated shows that the α-toc flip-flop rate is sensitive to bilayer lipid type. In particular, α-toc has a much lower flip-flop rate in a POPE bilayer compared to the three PC lipid bilayers due to the smaller area per lipid in the POPE bilayer. For DMPC and POPC, the α-toc flip-flop rates are significantly higher at higher α-toc concentration and this appears to be related to the local structural disruption caused by α-toc clusters spanning the bilayer.
使用分子动力学模拟，我们研究了α-生育酚（α-生育酚）与二棕榈酰磷脂酰胆碱（DPPC）、二肉豆蔻酰磷脂酰胆碱（DMPC）、棕榈酰油酰磷脂酰胆碱（POPC）和棕榈酰油酰磷脂酰乙醇胺（POPE）脂质双层的相互作用。目的是更好地了解α-生育酚在双层内的定位和取向；这些性质对α-生育酚的抗氧化活性具有重要意义。我们研究了含有 128 个脂质的双层系统，其中存在单个或 14 个α-生育酚分子。通过有偏分子动力学模拟研究了单个α-生育酚双层系统，其中获得了平均力势（PMF）和扩散系数作为α-生育酚头基团和双层中心之间距离的函数。使用无偏分子动力学模拟研究了较高α-生育酚浓度的系统。对于所有四个双层系统，在两种浓度下，模拟表明α-生育酚羟基的最可能位置就在脂质羰基下方。总体而言，模拟结果与现有实验数据吻合良好，除了 DMPC 双层系统，一些实验预测α-生育酚更靠近双层中心。计算得到的翻转频率表明，α-生育酚的翻转速率对双层脂质类型敏感。特别是，由于 POPE 双层中每个脂质的面积较小，与三种 PC 脂质双层相比，α-生育酚在 POPE 双层中的翻转速率要低得多。对于 DMPC 和 POPC，α-生育酚的翻转速率在较高α-生育酚浓度下显著增加，这似乎与α-生育酚簇跨越双层引起的局部结构破坏有关。
