Structural Mass Spectometry for protein modeling

用于蛋白质建模的结构质谱分析

• 批准号: 298351-2010
• 负责人: Schriemer, David
• 金额: $ 3.64万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=571482
• 关键词: Structural; Mass; Spectometry; protein; modeling

Determining the composition, assembly and dynamics of multi-protein complexes is essential for studying the function of many cellular processes we understand only at a crude level. There is a strong need for new technologies in this area, as these complexes represent a new frontier in drug discovery research. This proposal presents a strategy to develop and explore concepts in Structural Mass Spectrometry (SMS) as a way to model such complexes. SMS is an emerging field that combines "dynamic protein topology" measurements with computational methods, in order to obtain high resolution images. New advancements are needed to obtain these images at sufficient resolution to support detailed investigations into protein function. Unfortunately, mass spectrometry systems and methods have been developed for other applications, and don't readily apply to SMS. Through this research, we will develop new instruments, software and methods to harness the potential of SMS for protein imaging. Our goal is to develop techniques for "coding" protein structure and dynamics into quantities that the mass spectrometer can measure, and then translating these measurements by computer into accurate structural models. Successful completion of this program of studies will provide a powerful new tool for the life sciences, which can be used in basic research and by the pharmaceutical community, with the capacity to accelerate rates of drug discovery.

确定多蛋白复合物的组成、组装和动力学对于研究许多我们仅在粗略水平上了解的细胞过程的功能至关重要。这一领域迫切需要新技术，因为这些复合物代表了药物发现研究的新前沿。本提案提出了一种策略，以发展和探索结构质谱（SMS）的概念，作为一种模拟这种复合物的方法。SMS是一个新兴领域，它将“动态蛋白质拓扑”测量与计算方法相结合，以获得高分辨率图像。为了获得足够分辨率的这些图像，以支持对蛋白质功能的详细研究，需要取得新的进展。不幸的是，质谱系统和方法已经开发用于其他应用，并且不容易适用于SMS。通过这项研究，我们将开发新的仪器、软件和方法来利用SMS在蛋白质成像方面的潜力。我们的目标是开发一种技术，将蛋白质结构和动力学“编码”成质谱仪可以测量的数量，然后通过计算机将这些测量结果转化为精确的结构模型。该项目的成功完成将为生命科学提供一个强大的新工具，可用于基础研究和制药界，具有加速药物发现速度的能力。