Molecular dynamics simulations of homo-oligomeric bundles embedded within a lipid bilayer.
Molecular dynamics simulations of homo-oligomeric bundles embedded within a lipid bilayer.
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嵌入脂质双层内的同源寡聚束的分子动力学模拟。
DOI：
10.1016/j.bpj.2013.07.053
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发表时间：
2013
影响因子：
3.4
通讯作者：
Moore,PrestonB
中科院分区：
文献类型：
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作者：
Nguyen,ThuyHienT;Liu,Zhiwei;Moore,PrestonB
利用分子动力学模拟，我们研究了跨膜蛋白的结构、螺旋间相互作用和动力学。具体来说，我们研究了由具有序列 Ac-(LSSLLSL)3-NH2(LS2) 或 Ac-(LSSLLSL)3-NH2(LS3) 的合成 α-螺旋组成的同源寡聚螺旋束系统。 LS2 和 LS3 螺旋肽被设计为具有两亲特性，可在膜中形成离子通道。我们模拟了包含一到六个肽的束，这些肽嵌入棕榈酰油酰磷脂酰胆碱（POPC）脂质双层中并放置在两个水层之间。我们的目标是提供对两亲性螺旋肽如何相互作用以及它们在不同同源寡聚状态下的动力学行为的基本理解。为了了解结构特性，我们检查了螺旋长度、单个螺旋和整个螺旋束的倾斜角、螺旋间距离、螺旋间交叉角、螺旋疏水到亲水向量投影以及跨膜通道孔内的螺旋间亲水（丝氨酸-丝氨酸）接触的平均数量。为了分析动力学特性，我们计算了每个螺旋的旋转自相关函数以及相邻螺旋之间的旋转速度的互相关。观察到的结构和动力学特征表明，包含 4 至 6 个肽的高阶束由多个 1 至 3 个肽的低阶束组成。例如，发现 LS2 通道在由“二聚体的二聚体”组成的四聚体束中是稳定的。此外，我们观察到二聚体至四聚体系统中一对相邻螺旋之间至少存在两个强亲水接触，而五聚体和六聚体系统的螺旋对中仅存在一个强亲水螺旋间接触。我们相信这些结果是通用的，可以应用于更复杂的离子通道，从而深入了解离子通道的稳定性和组装。
Using molecular dynamics simulations, we studied the structure, interhelix interactions, and dynamics of transmembrane proteins. Specifically, we investigated homooligomeric helical bundle systems consisting of syntheticα-helices with either the sequence Ac-(LSLLLSL)3-NH2(LS2) or Ac-(LSSLLSL)3-NH2(LS3). The LS2 and LS3 helical peptides are designed to have amphipathic characteristics that form ion channels in membrane. We simulated bundles containing one to six peptides that were embedded in palmitoyl-oleoyl-phosphatidylcholine (POPC) lipid bilayer and placed between two lamellae of water. We aim to provide a fundamental understanding of how amphipathic helical peptides interact with each other and their dynamical behaviors in different homooligomeric states. To understand structural properties, we examined the helix lengths, tilt angles of individual helices and the entire bundle, interhelix distances, interhelix cross-angles, helix hydrophobic-to-hydrophilic vector projections, and the average number of interhelix hydrophilic (serine–serine) contacts lining the pore of the transmembrane channel. To analyze dynamical properties, we calculated the rotational autocorrelation function of each helix and the cross-correlation of the rotational velocity between adjacent helices. The observed structural and dynamical characteristics show that higher order bundles containing four to six peptides are composed of multiple lower order bundles of one to three peptides. For example, the LS2 channel was found to be stable in a tetrameric bundle composed of a "dimer of dimers." In addition, we observed that there is a minimum of two strong hydrophilic contacts between a pair of adjacent helices in the dimer to tetramer systems and only one strong hydrophilic interhelix contact in helix pairs of the pentamer and hexamer systems. We believe these results are general and can be applied to more complex ion channels, providing insight into ion channel stability and assembly.