标题： 用于描述多结构域蛋白质中拓扑耦合和机械对称性破缺的次序统计推断 显示英文标题

标题： Order statistics inference for describing topological coupling and mechanical symmetry breaking in multidomain proteins

摘要： 协同作用是蛋白质的显著特征，其中许多蛋白质表现出由离散结构域组成的模块化结构。 从蛋白质-蛋白质相互作用的多体性质来看，检测和描述结构区域之间的动态耦合是困难的。 通过利用基于GPU的计算加速，我们对作为多结构域蛋白质模型的全β-片层WW结构域的二聚体WW-WW进行了蛋白质强制展开的模拟。 我们发现，尽管物理上不相互作用的相同蛋白质结构域（WW）在低张力下表现出几乎对称的机械性能，这反映在它们的展开时间分布的相似性上，但当张力增加时，这些性能变得明显不同。 此外，在低拉力下无关联的展开过程在较高力下变得越来越相关（依赖）。 因此，施加的力不仅打破了“机械对称性”，还耦合了物理上不相互作用的蛋白质结构域，形成了多结构域蛋白质。 我们将这种效应称为“拓扑耦合”。 我们开发了一种新的理论，受秩序统计学的启发，用于表征多结构域蛋白质中的蛋白质-蛋白质相互作用。 该方法利用平方高斯模型，但也可以与其他用于展开时间分布的参数模型结合使用。 该形式化方法可以应用于单分子实验实验室，以探测多结构域蛋白质中的机械协同作用和结构域通信。 显示英文摘要

摘要： Cooperativity is a hallmark of proteins, many of which show a modular architecture comprising discrete structural domains. Detecting and describing dynamic couplings between structural regions is difficult in view of the many-body nature of protein-protein interactions. By utilizing the GPU-based computational acceleration, we carried out simulations of the protein forced unfolding for the dimer WW-WW of the all-beta-sheet WW domains used as a model multidomain protein. We found that while the physically non-interacting identical protein domains (WW) show nearly symmetric mechanical properties at low tension, reflected, e.g., in the similarity of their distributions of unfolding times, these properties become distinctly different when tension is increased. Moreover, the uncorrelated unfolding transitions at a low pulling force become increasingly more correlated (dependent) at higher forces. Hence, the applied force not only breaks "the mechanical symmetry" but also couples the physically non-interacting protein domains forming a multi-domain protein. We call this effect "the topological coupling". We developed a new theory, inspired by Order statistics, to characterize protein-protein interactions in multi-domain proteins. The method utilizes the squared-Gaussian model, but it can also be used in conjunction with other parametric models for the distribution of unfolding times. The formalism can be taken to the single-molecule experimental lab to probe mechanical cooperativity and domain communication in multi-domain proteins.