淀粉样纤维形成过程中饱和伸长的Hamilton动力学
Hamiltonian Dynamics of Saturated Elongation in Amyloid Fiber Formation
摘要：
伸长是淀粉样纤维生长的基本过程，其特征是纤维伸长速率与单体浓度呈线性关系。然而，在高浓度区域，经常观察到亚线性相关性，这可以通过普遍的饱和机制来解释。在本文中，我们模拟了饱和伸长过程中通过Michaelis-Menten的机制，这是由两个子步骤-非特异性缔合和解离的单体与纤维末端，随后的构象变化的相关单体，以适应自己的纤维结构。典型的饱和浓度被认为是$7-70μM$为A $β$ 40，$α$ -突触核蛋白等。此外，通过使用一种新的哈密顿制剂，分析解决方案，有效的弱和强饱和条件下构建和应用到原纤化动力学的$α$ -突触核蛋白和丝素。
英文摘要：
Elongation is a fundament process in amyloid fiber growth, which is normally characterized by a linear relationship between the fiber elongation rate and the monomer concentration. However, in high concentration regions, a sub-linear dependence was often observed, which could be explained by a universal saturation mechanism. In this paper, we modeled the saturated elongation process through a Michaelis-Menten like mechanism, which is constituted by two sub-steps -- unspecific association and dissociation of a monomer with the fibril end, and subsequent conformational change of the associated monomer to fit itself to the fibrillar structure. Typical saturation concentrations were found to be $7-70μM$ for A$β$40, $α$-synuclein and etc. Furthermore, by using a novel Hamiltonian formulation, analytical solutions valid for both weak and strong saturated conditions were constructed and applied to the fibrillation kinetics of $α$-synuclein and silk fibroin.
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