Role of Water Molecules and Helix Structure Stabilization in the Laser-Induced Disruption of Amyloid Fibrils Observed by Nonequilibrium Molecular Dynamics Simulations.
Role of Water Molecules and Helix Structure Stabilization in the Laser-Induced Disruption of Amyloid Fibrils Observed by Nonequilibrium Molecular Dynamics Simulations.
复制标题
通过非平衡分子动力学模拟观察到水分子和螺旋结构稳定性在激光诱导的淀粉样原纤维破坏中的作用。
DOI：
10.1021/acs.jpcb.0c11491
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发表时间：
2021
期刊：
影响因子：
3.3
通讯作者：
Kawasaki T.
中科院分区：
文献类型：
--
作者：
Okumura H;Itoh SG;Nakamura K;Kawasaki T.
水在生物分子结构的形成和破坏中起着至关重要的作用。破坏生物分子结构的机制被认为是水分子主动破坏氢键。然而，使用非平衡分子动力学模拟，其中淀粉样蛋白-β淀粉样蛋白纤维通过红外自由电子激光（IR-FEL）照射被破坏，我们发现了一种新的机制，其中水分子破坏蛋白质聚集体。在每一脉冲的激光照射下，纤维中由C → O和N-H形成的分子间氢键被破坏。在许多情况下，这些键在辐照后自发地重新形成。然而，当水分子碰巧进入C → O和N-H之间的差距时，它会抑制氢键的重新形成。这些位点成为规则排列的氢键中的缺陷，随着磨损的蔓延，分子间β折叠中的所有氢键都被破坏。水分子的这种作用与其他已知的机制完全不同。这种新的机制可以解释最近的实验表明，淀粉样纤维不会被激光照射在干燥条件下破坏。此外，我们发现淀粉样蛋白破坏后形成的螺旋结构更多;这是因为螺旋结构中的共振频率不同。本研究结果为IR-FEL在淀粉样变性治疗中的应用提供了理论依据。
Water plays a crucial role in the formation and destruction of biomolecular structures. The mechanism for destroying biomolecular structures was thought to be an active breaking of hydrogen bonds by water molecules. However, using nonequilibrium molecular dynamics simulations, in which an amyloid-β amyloid fibril was destroyed via infrared free-electron laser (IR-FEL) irradiation, we discovered a new mechanism, in which water molecules disrupt protein aggregates. The intermolecular hydrogen bonds formed by C═O and N–H in the fibril are broken at each pulse of laser irradiation. These bonds spontaneously re-form after the irradiation in many cases. However, when a water molecule happens to enter the gap between C═O and N–H, it inhibits the re-formation of the hydrogen bonds. Such sites become defects in the regularly aligned hydrogen bonds, from which all hydrogen bonds in the intermolecular β-sheet are broken as the fraying spreads. This role of water molecules is entirely different from other known mechanisms. This new mechanism can explain the recent experiments showing that the amyloid fibrils are not destroyed by laser irradiation under dry conditions. Additionally, we found that helix structures form more after the amyloid disruption; this is because the resonance frequency is different in a helix structure. Our findings provide a theoretical basis for the application of IR-FEL to the future treatment of amyloidosis.