Department of Physics, University of North Carolina at Charlotte, Charlotte, North Carolina, USA.
Biophys J. 2009 Dec 2;97(11):3000-9. doi: 10.1016/j.bpj.2009.09.013.
A complete description of protein structure and function must include a proper treatment of mechanisms that lead to cooperativity. The helix/coil transition serves as a simple example of a cooperative folding process, commonly described by a nucleation-propagation mechanism. The prevalent view is that coil structure must first form a short segment of helix in a localized region despite paying a free energy cost (nucleation). Afterward, helical structure propagates outward from the nucleation site. Both processes entail enthalpy-entropy compensation that derives from the loss in conformational entropy on helix formation with concomitant gain in favorable interactions. Nucleation-propagation models inherently assume that cooperativity arises from a sequential series of local events. An alternative distance constraint model asserts there is a direct link between available degrees of freedom and cooperativity through the nonadditivity in conformational entropy. That is, helix nucleation is a concerted manifestation of rigidity propagating through atomic structure. The link between network rigidity and nonadditivity of conformational entropy is shown in this study by solving the distance constraint model using a simple global constraint counting approximation. Cooperativity arises from competition between excess and deficiency in available degrees of freedom in the coil and helix states respectively.
蛋白质结构和功能的完整描述必须包括对导致协同作用的机制进行适当处理。螺旋/卷曲转变是一个简单的协同折叠过程的例子，通常用成核-传播机制来描述。普遍的观点是，尽管 coil 结构首先要在局部区域形成一段较短的 helix，这会付出自由能的代价（成核）。之后，螺旋结构从成核点向外传播。这两个过程都需要焓熵补偿，这是由 helix 形成过程中构象熵的损失以及有利相互作用的增加引起的。成核-传播模型本质上假定协同作用来自于一系列连续的局部事件。另一种距离约束模型则断言，通过构象熵的非加和性，自由度和协同作用之间存在直接联系。也就是说，helix 成核是通过原子结构传播的刚性的协同表现。在这项研究中，通过使用简单的全局约束计数近似值来解决距离约束模型，显示了网络刚性与构象熵非加和性之间的联系。协同作用来自于 coil 和 helix 状态中可用自由度的过剩和不足之间的竞争。
