According to the generalized conformational selection model, ligand binding involves the co-existence of at least two conformers with different ligand-affinities in a dynamical equilibrium. Conformational transitions between them should be guaranteed by intramolecular vibrational dynamics associated to each conformation. These motions are, therefore, related to the biological function of a protein. Positions whose mutations are found to alter these vibrations the most can be defined as key positions, that is, dynamically important residues that mediate the ligand-binding conformational change. In a previous study, we have shown that these positions are evolutionarily conserved. They correspond to buried aliphatic residues mostly localized in regular structured regions of the protein like β-sheets and α-helices. In the present paper, we perform a network analysis of these key positions for a large dataset of paired protein structures in the ligand-free and ligand-bound form. We observe that networks of interactions between these key positions present larger and more integrated networks with faster transmission of the information. Besides, networks of residues result that are robust to conformational changes. Our results reveal that the conformational diversity of proteins seems to be guaranteed by a network of strongly interconnected key positions rather than individual residues.

中文翻译：

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介导配体结合构象变化的蛋白质结构中动态重要残基的网络分析。

根据广义构象选择模型，配体结合涉及至少两个具有不同配体亲和力的构象体在动态平衡中共存。它们之间的构象转变应通过与每个构象相关的分子内振动动力学来保证。因此，这些运动与蛋白质的生物学功能有关。发现其突变最能改变这些振动的位置可以定义为关键位置，即，介导配体结合构象变化的动态重要残基。在先前的研究中，我们表明这些位置在进化上是保守的。它们对应于大部分位于蛋白质规则结构区域（如β-折叠和α-螺旋）中的掩埋脂族残基。在本文中，我们对无配体和配体结合形式的成对蛋白质结构的大型数据集进行了这些关键位置的网络分析。我们观察到，这些关键职位之间的互动网络呈现出更大，集成度更高的网络，信息传输速度更快。此外，产生的残基网络对构象变化具有鲁棒性。我们的结果表明，蛋白质的构象多样性似乎是由高度相互连接的关键位置而非单个残基组成的网络所保证的。残基网络对构象变化具有鲁棒性。我们的结果表明，蛋白质的构象多样性似乎是由高度相互连接的关键位置而非单个残基组成的网络所保证的。残基网络对构象变化具有鲁棒性。我们的结果表明，蛋白质的构象多样性似乎是由高度相互连接的关键位置而非单个残基组成的网络所保证的。