Modeling Amyloid Fibril Formation
Modeling Amyloid Fibril Formation
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DOI：
10.1134/s0006297911030114
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发表时间：
2011-03-01
影响因子：
2.8
通讯作者：
Galzitskaya, O. V.
中科院分区：
文献类型：
--
作者：
Dovidchenko, N. V.;Galzitskaya, O. V.
文献中尚未提出淀粉样蛋白结构形成过程中蛋白质重排的详细逐步模型。这项工作的目的是根据最新的实验数据设计一个动力学模型来描述淀粉样蛋白的形成过程。提出了一个通用动力学模型来描述淀粉样蛋白形成过程，包括连续单体附着到低聚物上的聚合成核机制以及淀粉样蛋白聚集体的自动催化生长，这意味着所有类型的指数生长，例如分支、断裂和从表面生长。计算机模拟表明，该模型正确描述了实验观察到的淀粉样原纤维的生长阶段，并且模型中指数生长阶段的存在对于模拟淀粉样原纤维的形成至关重要。该模型的关键特征是总量的指数增长阶段。这个阶段可以同时描述通过分支、分裂或从表面生长而导致的聚集体扩大的几个版本。使用该模型获得的数据得出了有关淀粉样原纤维组装中每个阶段的重要性的结论。
No detailed step-by-step model of protein rearrangements during amyloid structure formation has been presented in the literature. The aim of this work was to design a kinetic model for description of the amyloid formation process on the basis of the most recent experimental data. A general kinetic model is proposed for description of the amyloid formation process including the nucleation mechanism of polymerization with consecutive monomer attachment to oligomer and auto-catalytic growth of amyloid aggregates implying all types of exponential growth such as branching, fragmentation, and growth from the surface. Computer simulations have shown that the model correctly describes experimentally observed growth stages of amyloid fibrils and that the presence of exponential growth stage in the model is critical for modeling amyloid fibril formation. The key feature of the proposed model is the stage of the exponential growth of the aggregate. Such stage can simultaneously describe several versions of aggregate enlargement by branching, fragmentation, or growth from the surface. Data obtained using this model suggest conclusions concerning the significance of each stage in amyloid fibril assembly.