Amyloid Fibril Disruption by Ultrasonic Cavitation: Nonequilibrium Molecular Dynamics Simulations
Amyloid Fibril Disruption by Ultrasonic Cavitation: Nonequilibrium Molecular Dynamics Simulations
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DOI：
10.1021/ja502749f
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发表时间：
2014-07-30
影响因子：
15
通讯作者：
Itoh, Satoru G.
中科院分区：
文献类型：
--
作者：
Okumura, Hisashi;Itoh, Satoru G.
我们描述了超声波空化破坏阿尔茨海默氏症淀粉样β肽的淀粉样纤维。为此，我们进行了非平衡全原子分子动力学模拟与正弦压力和可视化的过程与电影。当压力为负时，通常在跨膜区的疏水残基处形成气泡。大多数β链在气泡中保持其二级结构。当压力变为正值时，气泡破裂，水分子撞击非跨膜区域的亲水残基，破坏淀粉样蛋白。较短的淀粉样蛋白需要较长的超声时间来破坏，因为它们没有足够的疏水残基作为核来形成气泡。这些结果与通过超声处理获得单分散淀粉样蛋白原纤维的实验一致。
We describe the disruption of amyloid fibrils of Alzheimer's amyloid-beta peptides by ultrasonic cavitation. For this purpose, we performed nonequilibrium all-atom molecular dynamics simulations with sinusoidal pressure and visualized the process with movies. When the pressure is negative, a bubble is formed, usually at hydrophobic residues in the transmembrane region. Most beta-strands maintain their secondary structures in the bubble. When the pressure becomes positive, the bubble collapses, and water molecules crash against the hydrophilic residues in the nontransmembrane region to disrupt the amyloid. Shorter amyloids require longer sonication times for disruption because they do not have enough hydrophobic residues to serve as a nucleus to form a bubble. These results agree with experiments in which monodispersed amyloid fibrils were obtained by ultrasonication.