论文标题
淀粉样纤维形成中饱和伸长的哈密顿动力学
Hamiltonian Dynamics of Saturated Elongation in Amyloid Fiber Formation
论文作者
论文摘要
伸长是淀粉样纤维生长的基础过程，通常其特征是纤维伸长率与单体浓度之间的线性关系。但是，在高浓度区域中，经常观察到亚线性依赖性，这可以通过通用饱和机制来解释。在本文中，我们通过Michaelis-Menten的机制对饱和的伸长过程进行了建模，该机制由两个子阶段组成 - 单体与原纤维端的非特异性关联和离解，以及相关单体的随后构象变化，以适应本身与原纤维结构。对于$β$ 40的典型饱和度浓度为$7-70μm$，$α$ -Synaclein等。此外，通过使用一种新型的哈密顿配方，对弱饱和条件有效的分析解决方案构建并应用于$α$ -Synnenucelein and Silk-Sellsfibroin的纤维化动力学。
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.
