EAGER: Development of a Modular Ion Mobility Mass Spectrometry System for Structural Biology

在化学测量和成像计划的支持下，华盛顿大学的布什教授开发了一种模块化离子迁移质谱仪(MIMMS)系统，使新的实验能够探索蛋白质和蛋白质络合物的溶液和气相结构。蛋白质自我组装成“分子机器”，使细胞能够执行原本无法实现的复杂功能。人们越来越需要补充的结构工具来确定蛋白质组的四级结构，而质谱学在满足这些未得到满足的需求方面发挥着越来越重要的作用。该研究计划通过为蛋白质和蛋白质复合体的多阶段表征提供新的、灵敏的仪器，并通过提供对蛋白质和蛋白质复合体在气相中的构象图景的基本见解，在天然MS领域产生重大影响，这可能在分析仪器、结构生物学和生物制药表征领域带来新的机会。布什教授还为研究生研究员提供跨学科培训机会，在自然质谱学和离子迁移率光谱学快速发展的领域中开发仪器和最先进的分析方法。研究目标是演示使用模块来塑造分离、捕获和塑造蛋白质和蛋白质复合体的选择离子，以及进行更高阶离子迁移率质谱学实验的模块网络。这些模块被组合在一起形成网络，这些网络可能会使新的实验成为可能，而使用现有的质谱仪是不可能的。这种方法的主要优点是，模块将共享尺寸、设计元素和驱动电子设备；独立于复杂的仪器进行单独改进；然后添加到模块网络中，而不会影响其他模块的功能。

With the support from the Chemical Measurement and Imaging Program, Professor Bush at the University Washington develops a Modular Ion Mobility Mass Spectrometry (MIMMS) system that enables new experiments to probe the solution and gas-phase structures of proteins and protein complexes. The self-assembly of proteins into 'molecular machines' enables cells to perform sophisticated functions that are otherwise inaccessible. There is a growing need for complementary structural tools to determine the quaternary structures of the proteome and mass spectrometry (MS) plays an increasingly important role in fulfilling these unmet needs. The research plan makes large impacts in the field of native MS by providing new, sensitive instrumentation for multistage characterization of proteins and protein complexes, and by providing fundamental insights into the conformational landscapes of proteins and protein complexes in the gas phase, which may lead to new opportunities in the fields of analytical instrumentation, structural biology, and characterization of biopharmaceuticals. Professor Bush also provides support to a graduate student researcher with interdisciplinary training opportunities on instrument development and state-of-the-art analytical method development in the rapidly growing fields of native mass spectrometry and ion mobility spectrometry.The research objectives are to demonstrate the use of modules to shape separate, trap, and shape select ions of proteins and protein complexes and networks of modules to perform higher-order ion mobility mass spectrometry experiments. These modules are combined to form networks that may enable new experiments that are not possible using existing mass spectrometry instruments. Key advantages of this approach are that the modules will share dimensions, design elements, and drive electronics; be individually refined independently from a complex instrument; and then be added to networks of modules, without compromising the capabilities of the other modules.