Structural and pathway complexity of β-strand reorganization within aggregates of human transthyretin(105-115) peptide
Structural and pathway complexity of β-strand reorganization within aggregates of human transthyretin(105-115) peptide
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DOI：
10.1021/jp0703051
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发表时间：
2007-05-17
影响因子：
3.3
通讯作者：
Huo, Shuanghong
中科院分区：
文献类型：
--
作者：
Li, Da-Wei;Han, Li;Huo, Shuanghong
用分子动力学（MD）和隐式溶剂化模型模拟了人甲状腺素运载蛋白肽（TTR（105-115））在二聚体聚集体中的链间构象重排，总长度为48 μ s。在MD模拟中采样的构象被聚类以识别自由能最小值，而没有自由能表面的任何投影。一个连接的图形构造与节点（=集群）和边缘对应的自由能最小值和节点之间的过渡，分别。该连通图反映了自由能表面的复杂性，用于提取过渡不连通图，该图反映了自由能最小值对之间的整体自由能势垒，但不包含过渡路径的信息。通过对原始图和分子动力学数据的进一步处理，得到了重要自由能极小值之间的跃迁路径。我们已经发现，平行和反平行的聚集填充。具有不同排列模式的平行聚集体被不可忽略的自由能势垒分开。链间构象重组存在多途径。大多数访问路线不占主导地位的动力学，而较少访问的路线贡献一点，但他们是众多的，他们的总贡献实际上是占主导地位的。有各种各样的爬行运动，包括通过β-凸起，侧链辅助爬行，以及由一条链形成的发夹的翻转或旋转。
Interstrand conformational rearrangements of human transthyretin peptide (TTR(105-115)) within dimeric aggregates were simulated by means of molecular dynamics (MD) with implicit solvation model for a total length of 48 mu s. The conformations sampled in the MD simulations were clustered to identify free energy minima without any projections of free energy surface. A connected graph was constructed with nodes (=clusters) and edges corresponding to free energy minima and transitions between nodes, respectively. This connected graph which reflects the complexity of the free energy surface was used to extract the transition disconnectivity graph, which reflects the overall free energy barriers between pairs of free energy minima but does not contain information on transition paths. The routes of transitions between important free energy minima were obtained by further processing the original graph and the MD data. We have found that both parallel and antiparallel aggregates are populated. The parallel aggregates with different alignment patterns are separated by nonnegligible free energy barriers. Multiroutes exist in the interstrand conformational reorganization. Most visited routes do not dominant the kinetics, while less visited routes contribute a little each but they are numerous and their total contributions are actually dominant. There are various kinds of reptation motions, including those through a beta-bulge, side-chain aided reptation, and flipping or rotation of a hairpin formed by one strand.