Koubi L, Tarek M, Klein M L, Scharf D
Center for Molecular Modeling, Department of Chemistry, University of Pennsylvania, Philadelphia 19104-6323, USA.
Biophys J. 2000 Feb;78(2):800-11. doi: 10.1016/S0006-3495(00)76637-9.
We report a 2-ns constant pressure molecular dynamics simulation of halothane, at a mol fraction of 50%, in the hydrated liquid crystal bilayer phase of dipalmitoylphosphatidylcholine. Halothane molecules are found to preferentially segregate to the upper part of the lipid acyl chains, with a maximum probability near the C(5) methylene groups. However, a finite probability is also observed along the tail region and across the methyl trough. Over 95% of the halothane molecules are located below the lipid carbonyl carbons, in agreement with photolabeling experiments. Halothane induces lateral expansion and a concomitant contraction in the bilayer thickness. A decrease in the acyl chain segment order parameters, S(CD), for the tail portion, and a slight increase for the upper portion compared to neat bilayers, are in agreement with several NMR studies on related systems. The decrease in S(CD) is attributed to a larger accessible volume per lipid in the tail region. Significant changes in the electric properties of the lipid bilayer result from the structural changes, which include a shift and broadening of the choline headgroup dipole (P-N) orientation distribution. Our findings reconcile apparent controversial conclusions from experiments on diverse lipid systems.
我们报告了在二棕榈酰磷脂酰胆碱的水合液晶双层相中，对摩尔分数为50%的氟烷进行的2纳秒恒压分子动力学模拟。发现氟烷分子优先聚集在脂质酰基链的上部，在C(5)亚甲基附近概率最大。然而，在尾部区域以及穿过甲基槽处也观察到一定概率。超过95%的氟烷分子位于脂质羰基碳以下，这与光标记实验结果一致。氟烷会导致双层横向扩张并伴随双层厚度收缩。与纯双层相比，尾部部分的酰基链段序参数S(CD)降低，上部略有增加，这与对相关体系的多项核磁共振研究结果一致。S(CD)的降低归因于尾部区域每个脂质的可及体积更大。脂质双层电学性质的显著变化源于结构变化，其中包括胆碱头部偶极(P-N)取向分布的偏移和展宽。我们的研究结果调和了不同脂质体系实验中明显相互矛盾的结论。
