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

在化学测量和成像项目的支持下，华盛顿大学的布什教授开发了一种模块化离子迁移率质谱（MIMMS）系统，使新的实验能够探测蛋白质和蛋白质复合物的溶液和气相结构。蛋白质自组装成“分子机器”，使细胞能够执行其他方式无法实现的复杂功能。越来越需要补充结构工具来确定蛋白质组的四级结构，质谱（MS）在满足这些未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物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物在气相中的构象景观的基本见解，在天然质谱领域产生重大影响，这可能会在分析仪器、结构生物学和生物制药表征领域带来新的机会。布什教授还为一名研究生研究员提供跨学科培训机会，在快速发展的天然质谱法和离子迁移率谱法领域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形成分离，捕获和形状选择离子的蛋白质和蛋白质复合物和模块网络，以执行高阶离子迁移质谱实验。这些模块组合起来形成网络，可以实现使用现有质谱仪器无法进行的新实验。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元件；独立于复杂的仪器进行单独的提炼；然后添加到模块网络中，而不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.