The native structures of proteins, except for notable exceptions of intrinsically disordered proteins, in general take their most stable conformation in the physiological condition to maintain their structural framework so that their biological function can be properly carried out. Experimentally, the stability of a protein can be measured by several means, among which the pulling experiment using the atomic force microscope (AFM) stands as a unique method. AFM directly measures the resistance from unfolding, which can be quantified from the observed force-extension profile. It has been shown that key features observed in an AFM pulling experiment can be well reproduced by computational molecular dynamics simulations. Here, we applied computational pulling for estimating the accuracy of computational protein structure models under the hypothesis that the structural stability would positively correlated with the accuracy, i.e. the closeness to the native, of a model. We used in total 4929 structure models for 24 target proteins from the Critical Assessment of Techniques of Structure Prediction (CASP) and investigated if the magnitude of the break force, that is, the force required to rearrange the model's structure, from the force profile was sufficient information for selecting near-native models. We found that near-native models can be successfully selected by examining their break forces suggesting that high break force indeed indicates high stability of models. On the other hand, there were also near-native models that had relatively low peak forces. The mechanisms of the stability exhibited by the break forces were explored and discussed.

中文翻译：

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使用引导分子动态张力评估计算蛋白质结构模型的质量


蛋白质的天然结构，除了本质上无序的蛋白质以外，一般在生理条件下会采取最稳定的构象，以维持其结构框架，从而使其生物学功能得以正常发挥。在实验上，可以通过多种方法测量蛋白质的稳定性，其中使用原子力显微镜（AFM）的拉伸实验是一种独特的方法。 AFM 直接测量展开的阻力，可以从观察到的力延伸曲线进行量化。事实证明，计算分子动力学模拟可以很好地再现 AFM 拉伸实验中观察到的关键特征。在这里，我们应用计算拉力来估计计算蛋白质结构模型的准确性，假设结构稳定性与模型的准确性（即与天然模型的接近程度）正相关。我们使用了来自结构预测技术关键评估 (CASP) 的 24 种目标蛋白的总共 4929 个结构模型，并研究了断裂力的大小，即重新排列模型结构所需的力，来自力分布的大小是否为足够的信息来选择接近本机的模型。我们发现，通过检查其断裂力可以成功选择接近原生的模型，这表明高断裂力确实表明模型具有高稳定性。另一方面，也有峰值力相对较低的近乎原生模型。对断裂力表现出的稳定性机制进行了探索和讨论。