Multiscale simulations and NMR spectroscopy of ubiquitin chains: linkage chemistry and chain behavior (B09*)

泛素链的多尺度模拟和核磁共振波谱：连接化学和链行为 (B09*)

• 批准号: 283755334
• 金额: --
• 依托单位: Arbeitsgruppe Theoretische und Computergestützte Chemie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/283755334?language=en
• 关键词: Multiscale; simulations; NMR; spectroscopy; ubiquitin

We aim at unravelling the intrinsic properties of differently linked ubiquitin chains which dictate the fate of ubiquitylated proteins. Structural and dynamic information on an atomistic level will be obtained by the synergistic application of high-resolution NMR spectroscopy and multiscale molecular dynamics simulation. One strength of the proposed work lies in the experimental accessibility of ubiquitin tri- and tetramers with highly specific isotopic labeling of individual ubiquitin moieties in the chain. Thus we will be able to investigate structural and dynamic properties, solvent accessibility, ligand binding and binding affinities specifically for each ubiquitin unit. Molecular interpretation of the NMR data and mechanistic insight into coupling of conformational behavior and interactions with binding partners will be provided by accompanying multiscale simulations. Our combined NMR spectroscopic / multiscale-simulation approach gives us a powerful new tool to investigate the existing variety of ubiquitylation and to obtain a better understanding of ubiquitylation as one fundamental proteostatic process.

我们的目标是解开内在的性质不同的连接泛素链决定的命运泛素化蛋白质。在原子水平上的结构和动力学信息将通过高分辨率NMR光谱和多尺度分子动力学模拟的协同应用获得。所提出的工作的一个优势在于泛素三聚体和四聚体在链中具有高度特异性的单个泛素部分的同位素标记的实验可及性。因此，我们将能够研究每个遍在蛋白单元的结构和动力学特性、溶剂可及性、配体结合和结合亲和力。伴随的多尺度模拟将提供NMR数据的分子解释和对构象行为和与结合伙伴的相互作用的耦合的机理洞察。我们结合NMR光谱/多尺度模拟方法为我们提供了一个强大的新工具来研究现有的各种泛素化，并获得更好的理解泛素化作为一个基本的蛋白质稳定过程。