Computer simulation of the folding–unfolding transition of island‐model proteins—folding pathway, transition process, and fluctuations
Computer simulation of the folding–unfolding transition of island‐model proteins—folding pathway, transition process, and fluctuations
复制标题
岛模型蛋白折叠-展开转变的计算机模拟——折叠途径、转变过程和波动
作者：
S. Segawa;T. Kawai
进行了Monte Carlo计算机模拟，以阐明岛模型蛋白质折叠和解折叠转变的动力学方面。根据骨架结构的特点，设计了五种不同类型的模型蛋白。计算机模拟清楚地表明，展开和折叠转变是N态和U态之间的全或无过程。它们是典型的Poisson过程。从速率常数的Arrhenius图，确定折叠和去折叠的活化能。此外，还确定了沿着反应坐标的折叠途径。沿着多肽链沿着形成几个局部结构几乎是同时发生的，但最可能的事件时间顺序存在于转变的时刻。这是最有可能的折叠途径。解折叠途径被认为是最可能的折叠途径的逆过程。考虑了各平衡态的波动与转变过程之间的关系。与绝对反应速率理论相反，瞬态沿反应坐标沿着分布较广。通过对“瞬态过程”的分析，我们试图确定瞬态过程开始的临界状态。结果，我们发现去折叠转变发生在N态附近的阶段。在U态期间，大的连接块很少出现，但它们出现在朝向N态的过渡过程中。然而，N-状态和U-状态之间的“分支点”位于N-状态附近，并且连接的块体倾向于在通过分支点之前展开。我们的结论是，后期折叠中间体的稳定性是重要的折叠途径的选择，而优先选择的早期折叠中间体是重要的折叠速率的加速。通过使用模型蛋白的计算机模拟来检查链内交联和肽片段结合对速率常数的影响。通常，通过交联形成的小尺寸环加速折叠速率，并且大尺寸环对天然构象的稳定性有很大贡献。我们还发现，肽段结合对剩余蛋白的折叠速率的加速贡献不大。
Monte Carlo computer simulations were performed to elucidate the dynamic aspects of the folding and unfolding transitions of island‐model protein. Five different types of model proteins were designed, according to characteristics of backbone structure. The computer simulations clearly show that the unfolding and folding transitions are all‐or‐none processes between the N‐and U‐states. They are typical Poisson processes. From the Arrhenius plots of rate constants, the activation enthalpies of folding and unfolding were determined. In addition, the folding pathways were determined along the reaction coordinate. Formations of several local structures along a polypeptide chain are almost simultaneous, but the most probable time sequence of events exists at the moment of transition. That is the most probable folding pathway. The unfolding pathway was found to be just the reverse process of the most probable folding pathway. The relationship between the fluctuations in each equilibrium state and the transition process was considered. In contrast to the theory of absolute reaction rate, the transient states are widely distributed along the reaction coordinate. From analysis of the “transient process,” we tried to determine the critical states from which the transient process starts. As a result, we found that the unfolding transition occurs at the stage near the N‐state. During the U‐state, large joined blocks rarely appear, but they appear in the transient process towards the N‐state. However, the “branch point” between the N‐ and U‐states lies near the N‐state, and joined blocks tend to unfold prior to passing over the branch point. We concluded that the stability of later folding intermediates is important for selection of the folding pathway, while preferential selection of an early folding intermediate is important in acceleration of the folding rate. The effects of intrachain cross‐linking and peptide fragment binding on the rate constants were examined by using computer simulations of model proteins. In general, a small‐sized loop formed by cross‐linking accelerates the folding rate and a large‐sized loop contributes much to the stabilization of the native conformation. We also found that peptide fragment binding contributes little to the acceleration of the folding rate of the residual protein.
核糖核酸酶 A 解折叠和重折叠过程中脯氨酸 93 的异构化。
影响因子：
2.9
作者：
Lin,LN;Brandts,JF
通讯作者：
Brandts,JF