Allosteric communication is the basis of signaling and information transfer. Collective interactions between amino acid residues, which are spatially distributed in the three dimensional structure of a protein molecule, form the basis of allosteric network. While the construction of residue interaction graphs (RIG) is based on static crystal structures of proteins, it is important to extract information on protein dynamics to understand allostery. Therefore, quantitative analysis of RIG based on the framework of differential network (DN), is immensely helpful in identifying key amino acid residue interactions within such communication pathways. While the simultaneous availability of protein structures from two different states is essential for DN, there are additional challenges. Crystallographic artifacts like nonbiological dimeric arrangements within the crystal lattice automatically influence the construction and eventually the interpretation of RIG. Therefore, experimental validation of predictions from the analyses of RIG is naturally scarce in the literature. Herein, we study the photo sensor domain of the signaling photoreceptor transcription factor, aureochrome1, to understand light‐driven signaling. We perform direct experiments to verify the predictions from RIG using the machinery of DN. However, the agreement leaves scope for improvement. We then discuss the notion of quaternary structure alignment to obtain a biologically meaningful dimer. Thence, we reconstruct the RIG and reanalyze the modified structure. Results of these reanalyses render far superior agreement with experiments. Therefore, this notion of addressing crystallographic biases provides a fresh yet general approach for reconciliation of theory and experiments. It is applicable beyond the present case to all signaling proteins in general.

中文翻译：

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Vaucheria aureochrome1光-氧-电压中的残基相互作用动力学：桥接理论和实验。

变构通讯是信号和信息传递的基础。在蛋白质分子的三维结构中空间分布的氨基酸残基之间的集体相互作用形成了变构网络的基础。虽然残基相互作用图（RIG）的构建是基于蛋白质的静态晶体结构，但提取蛋白质动力学信息以了解变构非常重要。因此，基于差分网络（DN）框架对RIG进行定量分析，有助于识别此类通信途径中关键的氨基酸残基相互作用。虽然DN必不可少的是同时获得来自两个不同状态的蛋白质结构，但仍存在其他挑战。晶格内的晶体伪像（例如非生物二聚体排列）会自动影响结构，并最终影响RIG的解释。因此，文献中自然缺乏对RIG分析进行预测的实验验证。在此，我们研究信号感光转录因子aureochrome1的光传感器域，以了解光驱动信号。我们使用DN的机器进行直接实验以验证RIG的预测。但是，该协议仍有改进的余地。然后，我们讨论四元结构比对的概念以获得生物学上有意义的二聚体。因此，我们重建RIG并重新分析修改后的结构。这些重新分析的结果与实验相吻合。因此，解决晶体学偏见的这一概念为理解理论和实验提供了一种新颖而又通用的方法。除了当前情况，它通常还适用于所有信号蛋白。