Structures of Gas-Phase Protein Ions

气相蛋白离子的结构

• 批准号: 0078737
• 负责人: David Clemmer
• 金额: $ 37.44万
• 依托单位: Indiana University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-15 至 2005-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0078737&HistoricalAwards=false
• 关键词: Structures; Gas; Phase; Protein; Ions

This research program entitled "Structures of Gas-Phase Protein Ions" represents a significant expansion of the prior work of Dr. David Clemmer of Indiana University at Bloomington and is supported by the Analytical and Surface Chemistry program. The goal of this research is to investigate the 3-dimensional conformation of gas-phase proteins and peptides using a modified ion mobility/time of flight mass spectrometer. The instrumentation to be used can accommodate a high number of analyses, which will enable the screening of large libraries of compounds. Chemical probes, such as hydrogen-deuterium (H/D) exchange reactions, will be used to investigate both conformation and reactivity. The novel experiments planned, which couple H/D exchange studies with collision induced dissociation experiments, may result in an important new technique for interpreting and measuring H/D exchange data. The correlation between solution phase and gas phase protein conformations is not well defined, and may not be similar to solution phase conformations. However, if a correlation is found, this research could have a major impact on the understanding of the chemical mechanisms of biological reactivity and the study of protein structure/reactivity relationships. With the increased understanding of the role of proteins in biological systems, it is now known that the 3-dimensional structure of a protein directly effects the function to be performed by the protein. Thus, an important area of chemical research today is the development of techniques to establish the 3-dimensional structure. In this fundamental research by Professor Clemmer, he will develop a new technique to examine protein structure. This research, though high risk, has the potential to impact society in the future through improved understanding of disease mechanisms based on protein structure/function relationships. This will lead to enhancements in pharmaceutical development and treatment of disease.

这项名为“气相蛋白离子结构”的研究项目是对印第安纳大学布卢明顿分校 David Clemmer 博士之前工作的重大扩展，并得到了分析和表面化学项目的支持。 本研究的目标是使用改进的离子淌度/飞行时间质谱仪研究气相蛋白质和肽的 3 维构象。 所使用的仪器可以进行大量分析，这将能够筛选大型化合物库。 化学探针，例如氢-氘（H/D）交换反应，将用于研究构象和反应性。 计划中的新实验将 H/D 交换研究与碰撞诱导解离实验结合起来，可能会产生一种解释和测量 H/D 交换数据的重要新技术。 溶液相和气相蛋白质构象之间的相关性尚未明确定义，并且可能与溶液相构象不相似。 然而，如果发现相关性，这项研究可能会对生物反应性化学机制的理解和蛋白质结构/反应性关系的研究产生重大影响。 随着对蛋白质在生物系统中的作用的了解不断加深，现在已知蛋白质的 3 维结构直接影响蛋白质所执行的功能。因此，当今化学研究的一个重要领域是开发建立三维结构的技术。 在克莱默教授的这项基础研究中，他将开发一种检查蛋白质结构的新技术。 这项研究虽然风险较高，但通过提高对基于蛋白质结构/功能关系的疾病机制的理解，有可能在未来影响社会。 这将导致药物开发和疾病治疗的加强。