Nonlinear elasticity, proteinquakes, and the energy landscapes of functional transitions in proteins
Nonlinear elasticity, proteinquakes, and the energy landscapes of functional transitions in proteins
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DOI：
10.1073/pnas.2135471100
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发表时间：
2003-10-28
影响因子：
11.1
通讯作者：
Wolynes, PG
中科院分区：
文献类型：
--
作者：
Miyashita, O;Onuchic, JN;Wolynes, PG
生物分子的大规模运动涉及沿低频正常模式的线性弹性变形，但对于函数来说，非线性至关重要。此外，与宏观机器不同，生物机器可以在功能过程中局部断裂然后重新组装。我们提出了一个全局结构转变的模型，例如变构，涉及大规模运动和可能的部分展开，说明了腺苷酸激酶构象转变的方法。打开和关闭状态之间的结构变形通过单独的反应物和产物表面上的低频模式发生，当能量有利时从一种状态切换到另一种状态。切换模型是最直接的非谐波插值，它允许通过线性正常模式计算来估计过程的障碍，而线性正常模式计算本身不能用于激活事件。局部展开或开裂发生在转变过程中弹性应力变得过高的区域。裂解会导致添加的变性剂对变构酶功能产生违反直觉的催化作用。它还导致平衡常数和速率之间存在不寻常的关系，就像最近在运动蛋白的单分子实验中看到的那样。
Large-scale motions of biomolecules involve linear elastic deformations along low-frequency normal modes, but for function nonlinearity is essential. In addition, unlike macroscopic machines, biological machines can locally break and then reassemble during function. We present a model for global structural transformations, such as allostery, that involve large-scale motion and possible partial unfolding, illustrating the method with the conformational transition of adenylate kinase. Structural deformation between open and closed states occurs via low-frequency modes on separate reactant and product surfaces, switching from one state to the other when energetically favorable. The switching model is the most straightforward anharmonic interpolation, which allows the barrier for a process to be estimated from a linear normal mode calculation, which by itself cannot be used for activated events. Local unfolding, or cracking, occurs in regions where the elastic stress becomes too high during the transition. Cracking leads to a counterintuitive catalytic effect of added denaturant on allosteric enzyme function. It also leads to unusual relationships between equilibrium constant and rate like those seen recently in single-molecule experiments of motor proteins.