论文标题

AB40和AB42的蛋白质聚集和分子拥挤作用的随机动力学研究

Stochastic Kinetic Study of Protein Aggregation and Molecular Crowding Effects of Ab40 and Ab42

论文作者

Bridstrup, John, Yuan, Jian-Min, Schreck, John S.

论文摘要

β淀粉样蛋白肽AB40和AB42的两种同工型仅在AB42结束时的最后两个氨基酸IA中彼此不同。但是,它们在诱导阿尔茨海默氏病(AD)的能力上有很大差异。在体外实验中已经测量了AB40和AB42的原纤维生长的速率曲线以及分子拥挤的影响。另一方面,这些实验曲线已通过使用速率方程方法的基本反应步骤的速率常数拟合。文献中已经报道了几组此类速率参数。我们采用了在基于浏览器的模拟器Popsim中实现的最近开发的随机动力学方法,我们研究以揭示这些速率参数集所隐含的动力学行为差异。特别是,随机方法用于区分AB40和AB42同工型之间的动力学行为。结果,我们对这些速率参数集的有用性做出了一般性评论。

Two isoforms of beta amyloid peptides, Ab40 and Ab42, differ from each other only in the last two amino acids, IA, at the end of Ab42. They, however, differ significantly in their ability in inducing Alzheimer's disease (AD). The rate curves of fibril growth of Ab40 and Ab42 and the effects of molecular crowding have been measured in in vitro experiments. These experimental curves, on the other hand, have been fitted in terms of rate constants for elementary reaction steps using rate equation approaches. Several sets of such rate parameters have been reported in the literature. Employing a recently developed stochastic kinetic method, implemented in a browser-based simulator, popsim, we study to reveal the differences in the kinetic behaviors implied by these sets of rate parameters. In particular, the stochastic method is used to distinguish the kinetic behaviors between Ab40 and Ab42 isoforms. As a result, we make general comments on the usefulness of these sets of rate parameters.

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