Elongation dynamics of amyloid fibrils: A rugged energy landscape picture
Elongation dynamics of amyloid fibrils: A rugged energy landscape picture
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DOI：
10.1103/physreve.80.041906
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发表时间：
2009-10-01
影响因子：
2.4
通讯作者：
Vaux, David J.
中科院分区：
文献类型：
--
作者：
Lee, Chiu Fan;Loken, James;Vaux, David J.
蛋白质淀粉样原纤维是一种线性蛋白质聚集体，与许多神经退行性疾病有关。在这里，我们通过对粗粒度肽模型进行 Langevin 动态模拟来研究淀粉样蛋白原纤维伸长的动力学。我们的模拟结果表明，由于单体-原纤维相互作用受挫，伸长过程由一系列局部最小值主导。这种崎岖的能量景观图表明，与传统的两步伸长模型相比，原纤维化之前原纤维末端的单体回收量大大减少。这张图片以及讨论的其他预测可以用当前的实验技术进行测试。
Protein amyloid fibrils are a form of linear protein aggregates that are implicated in many neurodegenerative diseases. Here, we study the dynamics of amyloid fibril elongation by performing Langevin dynamic simulations on a coarse-grained model of peptides. Our simulation results suggest that the elongation process is dominated by a series of local minimum due to frustration in monomer-fibril interactions. This rugged energy landscape picture indicates that the amount of recycling of monomers at the fibrils' ends before being fibrilized is substantially reduced in comparison to the conventional two-step elongation model. This picture, along with other predictions discussed, can be tested with current experimental techniques.