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（MIMMS）系统，该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法无法实现的复杂功能。人们越来越需要互补的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仪器，并通过提供对气相中蛋白质和蛋白质复合物构象景观的基本见解，在天然MS领域产生了巨大影响，这可能会导致分析仪器，结构生物学和生物制药表征领域的新机会。Bush教授还为一名研究生研究员提供跨学科培训机会，在快速发展的本土质谱和离子迁移谱领域进行仪器开发和最先进的分析方法开发。研究目标是展示使用模块来形成分离，捕获，并对蛋白质和蛋白质复合物的离子以及模块的网络进行形状选择，以进行更高阶的离子迁移质谱实验。这些模块组合在一起形成网络，可以实现使用现有质谱仪器无法实现的新实验。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.