Large-scale conformational changes of proteins, including the open–closed transitions, are crucial for a variety of protein functions. These open–closed transitions are often associated with ligand binding. However, the understandings of the underlying mechanisms of the conformational changes within proteins during the open–closed transitions are still challenging at present. In this study, we quantified the intrinsic underlying conformational energy landscapes of five different proteins with large-scale open–closed transitions. This is realized by exploring the underlying density of states and the intrinsic conformational energy landscape topography measure Λ. Λ is a dimensionless ratio of conformational energy gap δE versus conformational energy roughness δE and configurational entropy S or size of the intrinsic conformational energy landscape. By quantifying the Λ of intrinsic open–closed conformational (Λ^oc) and intrinsic global folding (Λ^global) energy landscapes, we show that both intrinsic open–closed conformation energy and entropy landscapes are funneled toward the closed state. Furthermore, our results indicate the strong correlations between Λ and thermodynamics (conformational state transition temperature against trapping temperature) as well as between Λ and kinetics (open–closed kinetic time) of these proteins. This shows that the intrinsic conformational landscape topography determines both the conformational thermodynamic stability and kinetic speed of the conformational dynamics. Our investigations provide important insights for understanding the fundamental mechanisms of the protein conformational dynamics in a physical and global way.

中文翻译：

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定量分析具有大规模开放-闭合过渡的蛋白质的固有构象能景观

蛋白质的大规模构象变化，包括开-闭过渡，对于多种蛋白质功能至关重要。这些开闭转换通常与配体结合有关。然而，目前对蛋白质在开放-封闭转换过程中构象变化的潜在机制的理解仍然充满挑战。在这项研究中，我们量化了具有大规模开放-闭合过渡的五种不同蛋白质的内在潜在构象能图。这是通过探索潜在的状态密度和内在构象能量景观地形测度Λ来实现的。Λ是构象能隙δE与构象能粗糙度的无量纲比δE和构型熵S或内在构象能图的大小。通过定量内在开放-封闭的构象（Λ的Λ ^OC）和内在全球折叠（Λ^全球）能量图，我们表明内在的开闭构象能量和熵图都朝着闭合状态漏斗。此外，我们的结果表明Λ与这些蛋白质的热力学（构象状态转变温度对捕获温度）之间以及Λ与动力学（这些蛋白的开闭时间）之间具有很强的相关性。这表明固有构象景观地形决定了构象热力学稳定性和构象动力学的动力学速度。我们的研究为以物理和全局方式了解蛋白质构象动力学的基本机制提供了重要的见识。