Lopez Carlos F, Nielsen Steve O, Ensing Bernd, Moore Preston B, Klein Michael L
Center for Molecular Modeling and Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Biophys J. 2005 May;88(5):3083-94. doi: 10.1529/biophysj.104.053769. Epub 2005 Feb 18.
A cylindrical transmembrane molecule is constructed by linking hydrophobic sites selected from a coarse grain model. The resulting hollow tube assembly serves as a representation of a transmembrane channel, pore, or a carbon nanotube. The interactions of a coarse grain di-myristoyl-phosphatidyl-choline hydrated bilayer with both a purely hydrophobic tube and a tube with hydrophilic caps are studied. The hydrophobic tube rotates in the membrane and becomes blocked by lipid tails after a few tens of nanoseconds. The hydrophilic sites of the capped tube stabilize it by anchoring the tube in the lipid headgroup/water interfacial region of each membrane leaflet. The capped tube remains free of lipid tails. The capped tube spontaneously conducts coarse grain water sites; the free-energy profile of this process is calculated using three different methods and is compared to the barrier for water permeation through the lipid bilayer. Spontaneous tube insertion into an undisturbed lipid bilayer is also studied, which we reported briefly in a previous publication. The hydrophobic tube submerges into the membrane core in a carpetlike manner. The capped tube laterally fuses with the closest leaflet, and then, after plunging into the membrane interior, rotates to assume a transbilayer orientation. Two lipids become trapped at the end of the tube as it penetrates the membrane. The hydrophilic headgroups of these lipids associate with the lower tube cap and assist the tube in crossing the interior of the membrane. When the rotation is complete these lipids detach from the tube caps and fuse with the lower leaflet lipids.
通过连接从粗粒模型中选择的疏水位点构建圆柱形跨膜分子。所得的中空管组件可作为跨膜通道、孔或碳纳米管的一种表示。研究了粗粒二肉豆蔻酰磷脂酰胆碱水合双层与纯疏水管道以及带有亲水帽的管道之间的相互作用。疏水管道在膜中旋转，几十纳秒后被脂质尾部阻塞。带帽管道的亲水位点通过将管道锚定在每个膜小叶的脂质头部基团/水界面区域来使其稳定。带帽管道没有脂质尾部。带帽管道自发地传导粗粒水位点；使用三种不同方法计算该过程的自由能分布，并将其与水透过脂质双层的势垒进行比较。还研究了管道自发插入未受干扰的脂质双层的情况，我们在之前的一篇出版物中对此进行了简要报道。疏水管道以地毯状方式沉入膜核心。带帽管道与最靠近的小叶横向融合，然后在插入膜内部后旋转以呈现跨双层方向。当管道穿透膜时，两种脂质被困在管道末端。这些脂质的亲水头部基团与较低的管道帽结合，并协助管道穿过膜内部。旋转完成后，这些脂质从管道帽上脱离并与下层小叶脂质融合。
