Understanding of protein conformational dynamics is essential for elucidating molecular origins of protein structure–function relationship. Traditionally, reaction coordinates, i.e., some functions of protein atom positions and velocities have been used to interpret the complex dynamics of proteins obtained from experimental and computational approaches such as molecular dynamics simulations. However, it is nontrivial to identify the reaction coordinates a priori even for small proteins. Here, we evaluate the power of evolutionary couplings (ECs) to capture protein dynamics by exploring their use as reaction coordinates, which can efficiently guide the sampling of a conformational free energy landscape. We have analyzed 10 diverse proteins and shown that a few ECs are sufficient to characterize complex conformational dynamics of proteins involved in folding and conformational change processes. With the rapid strides in sequencing technology, we expect that ECs could help identify reaction coordinates a priori and enhance the sampling of the slow dynamical process associated with protein folding and conformational change.

中文翻译：

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使用进化耦合表征蛋白质的构象动力学

了解蛋白质构象动力学对于阐明蛋白质结构与功能关系的分子起源至关重要。传统上，反应坐标（即蛋白质原子位置和速度的某些功能）已用于解释从实验和计算方法（例如分子动力学模拟）获得的蛋白质的复杂动力学。然而，即使对于小蛋白质，先验地识别反应坐标也不是一件容易的事。在这里，我们通过探索进化耦合（EC）用作反应坐标的方法来评估进化耦合（EC）捕获蛋白质动力学的能力，这可以有效地指导构象自由能景观的采样。我们已经分析了10种不同的蛋白质，并表明一些EC足以表征参与折叠和构象变化过程的蛋白质的复杂构象动力学。随着测序技术的飞速发展，我们期望EC可以帮助先验识别反应坐标，并增强与蛋白质折叠和构象变化相关的缓慢动力学过程的采样。