Concentration effects of volatile anesthetics on the properties of model membranes: A coarse-grain approach
Concentration effects of volatile anesthetics on the properties of model membranes: A coarse-grain approach
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DOI：
10.1529/biophysj.104.044354
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发表时间：
2005-03-01
影响因子：
3.4
通讯作者：
Klein, ML
中科院分区：
文献类型：
--
作者：
Pickholz, M;Saiz, L;Klein, ML
为了深入了解药物作用在膜位点的分子水平机制，我们已经进行了广泛的分子动力学模拟的模型膜在挥发性麻醉剂的存在下，使用粗粒模型。已经研究了六种不同的麻醉剂（氟烷）/脂质（二肉豆蔻酰磷脂酰胆碱）比例，超出了医疗应用的典型低剂量。将挥发性麻醉剂引入预组装的完全水合的512分子脂质双层中，并且使用NPT系综在环境条件下进行每个分子动力学模拟。每脂质的面积单调增加与氟烷浓度和片层间距减小，而脂质双层厚度显示没有明显的差异，只有轻微的增加时，添加氟烷。麻醉剂分子的密度分布显示出沿着膜法线的双峰分布，最大值位于接近脂质-水界面区域。我们研究了氟烷分子。在双峰分布的两个最大值之间波动，并且我们在低和高麻醉剂浓度下观察到不同的机制。通过对脂质尾部重定向运动的研究，我们发现麻醉剂分子增加了靠近膜表面的脂质的链段顺序。
To gain insights into the molecular level mechanism of drug action at the membrane site, we have carried out extensive molecular dynamics simulations of a model membrane in the presence of a volatile anesthetic using a coarse-grain model. Six different anesthetic ( halothane)/lipid ( dimyristoylphosphatidylcholine) ratios have been investigated, going beyond the low doses typical of medical applications. The volatile anesthetics were introduced into a preassembled fully hydrated 512-molecule lipid bilayer and each of the molecular dynamics simulations were carried out at ambient conditions, using the NPT ensemble. The area per lipid increases monotonically with the halothane concentration and the lamellar spacing decreases, whereas the lipid bilayer thickness shows no appreciable differences and only a slight increase upon addition of halothane. The density profiles of the anesthetic molecules display a bimodal distribution along the membrane normal with maxima located close to the lipid-water interface region. We have studied how halothane molecules. uctuate between the two maxima of the bimodal distribution and we observed a different mechanism at low and high anesthetic concentrations. Through the investigation of the reorientational motions of the lipid tails, we found that the anesthetic molecules increase the segmental order of the lipids close to the membrane surface.