Protein sequence determines its structure and function. The indirect relationship between protein function and structure lies deep-rooted in the structural topology that has evolved into performing optimal function. The evolution of structure and its interconnectivity has been conventionally studied by comparing the root means square deviation between protein structures at the backbone level. Two factors that are necessary for the quantitative comparison of non-covalent interactions are (a) explicit inclusion of the coordinates of side-chain atoms and (b) consideration of multiple structures from the conformational landscape to account for structural variability. We have recently addressed these fundamental issues by investigating the alteration of inter-residue interactions across an ensemble of protein structure networks through a graph spectral approach. In this study, we have developed a rigorous method to compare the structure networks of homologous proteins, with a wide range of sequence identity percentages. A range of dissimilarity measures that show the extent of change in the network across homologous structures are generated, which also includes the comparison of the protein structure variability. We discuss in detail, scenarios where the variation of structure is not accompanied by loss or gain of the overall network and its vice versa. The sequence-based phylogeny among the homologs is also compared with the lineage obtained from information from such a robust structure comparison. In summary, we can obtain a quantitative comparison score for the structure networks of homologous proteins, which also enables us to study the evolution of protein function based on the variation of their topologies.

中文翻译：

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同源蛋白质结构网络的比较

蛋白质序列决定其结构和功能。蛋白质功能和结构之间的间接关系根深蒂固地存在于已进化为执行最佳功能的结构拓扑中。传统上通过比较主链水平上蛋白质结构之间的均方根偏差来研究结构的演化及其互连性。定量比较非共价相互作用所必需的两个因素是（a）明确包含侧链原子的坐标和（b）考虑构象景观中的多种结构以解释结构变异性。我们最近通过图谱方法研究了整个蛋白质结构网络中残基间相互作用的改变，解决了这些基本问题。在这项研究中，我们开发了一种严格的方法来比较同源蛋白质的结构网络，具有广泛的序列同一性百分比。生成了一系列显示同源结构网络变化程度的相异性度量，其中还包括蛋白质结构变异性的比较。我们详细讨论结构变化不伴随整个网络损失或增益的场景，反之亦然。同源物之间基于序列的系统发育也与从这种稳健的结构比较的信息获得的谱系进行比较。综上所述，我们可以获得同源蛋白质结构网络的定量比较分数，这也使我们能够根据其拓扑的变化来研究蛋白质功能的进化。