Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan.
J Chem Phys. 2013 Dec 14;139(22):225103. doi: 10.1063/1.4838476.
An intrinsically disordered protein (IDP) lacks a stable three-dimensional structure, while it folds into a specific structure when it binds to a target molecule. In some IDP-target complexes, not all target binding surfaces are exposed on the outside, and intermediate states are observed in their binding processes. We consider that stepwise target recognition via intermediate states is a characteristic of IDP binding to targets with "hidden" binding sites. To investigate IDP binding to hidden target binding sites, we constructed an IDP lattice model based on the HP model. In our model, the IDP is modeled as a chain and the target is modeled as a highly coarse-grained object. We introduced motion and internal interactions to the target to hide its binding sites. In the case of unhidden binding sites, a two-state transition between the free states and a bound state is observed, and we consider that this represents coupled folding and binding. Introducing hidden binding sites, we found an intermediate bound state in which the IDP forms various structures to temporarily stabilize the complex. The intermediate state provides a scaffold for the IDP to access the hidden binding site. We call this process multiform binding. We conclude that structural flexibility of IDPs enables them to access hidden binding sites and this is a functional advantage of IDPs.
无规蛋白（IDP）缺乏稳定的三维结构，但当它与靶分子结合时，会折叠成特定的结构。在一些 IDP-靶标复合物中，并非所有的靶标结合表面都暴露在外部，并且在它们的结合过程中观察到中间状态。我们认为，通过中间状态逐步识别靶标是 IDP 与具有“隐藏”结合位点的靶标结合的特征。为了研究 IDP 与隐藏靶标结合位点的结合，我们基于 HP 模型构建了一个 IDP 晶格模型。在我们的模型中，IDP 被建模为一个链，而靶标被建模为一个高度粗粒化的物体。我们为靶标引入了运动和内部相互作用来隐藏其结合位点。在无隐藏结合位点的情况下，观察到自由态和结合态之间的两态跃迁，我们认为这代表了耦合折叠和结合。引入隐藏结合位点后，我们发现了一个中间结合态，其中 IDP 形成各种结构以暂时稳定复合物。中间状态为 IDP 提供了一个支架来访问隐藏的结合位点。我们称这个过程为多样结合。我们得出结论，IDP 的结构灵活性使它们能够访问隐藏的结合位点，这是 IDP 的一个功能优势。
