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A protocol to automatically calculate homo-oligomeric protein structures through the integration of evolutionary constraints and NMR ambiguous contacts.
Computational and Structural Biotechnology Journal ( IF 6 ) Pub Date : 2019-12-26 , DOI: 10.1016/j.csbj.2019.12.002
Davide Sala 1 , Linda Cerofolini 2 , Marco Fragai 1, 3 , Andrea Giachetti 2 , Claudio Luchinat 1, 3 , Antonio Rosato 1, 3
Affiliation  

Protein assemblies are involved in many important biological processes. Solid-state NMR (SSNMR) spectroscopy is a technique suitable for the structural characterization of samples with high molecular weight and thus can be applied to such assemblies. A significant bottleneck in terms of both effort and time required is the manual identification of unambiguous intermolecular contacts. This is particularly challenging for homo-oligomeric complexes, where simple uniform labeling may not be effective. We tackled this challenge by exploiting coevolution analysis to extract information on homo-oligomeric interfaces from NMR-derived ambiguous contacts. After removing the evolutionary couplings (ECs) that are already satisfied by the 3D structure of the monomer, the predicted ECs are matched with the automatically generated list of experimental contacts. This approach provides a selection of potential interface residues that is used directly in monomer–monomer docking calculations. We validated the protocol on tetrameric L-asparaginase II and dimeric Sod1.



中文翻译:

一种通过整合进化约束和 NMR 模糊接触来自动计算同源寡聚蛋白质结构的协议。

蛋白质组装涉及许多重要的生物过程。固态核磁共振(SSNMR)光谱是一种适合高分子量样品结构表征的技术,因此可应用于此类组件。所需精力和时间方面的一个重要瓶颈是手动识别明确的分子间接触。这对于同源寡聚复合物来说尤其具有挑战性,因为简单的统一标记可能无效。我们通过利用协同进化分析从 NMR 衍生的模糊接触中提取同源寡聚界面的信息来应对这一挑战。去除单体 3D 结构已满足的进化耦合 (EC) 后,预测的 EC 与自动生成的实验接触列表进行匹配。这种方法提供了一系列潜在的界面残基,可直接用于单体-单体对接计算。我们验证了四聚体 L-天冬酰胺酶 II 和二聚体 Sod1 的方案。

更新日期:2019-12-26
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