Rapid ultra-sensitive three dimensional protein structure determination by mass s

描述(申请人提供)：蛋白质结构与细胞的正常功能直接相关，并提供对与健康或疾病相关的生化途径的分子水平的了解。该项目将开发一种检测气相中蛋白质结构的方法。这将通过使用能够产生新的蛋白质自由基的可调谐UV激光来修改最先进的质谱计来实现。观察这些自由基蛋白质的解离模式将揭示一系列距离限制，这些限制可以在分子动力学模拟的帮助下形成三维结构。这种方法将使快速、灵敏和灵活的优势被高度优化，用于蛋白质的质谱分析，应用于具有挑战性的结构确定领域。因此，许多传统方法难以处理的靶蛋白现在将成为结构阐明的有效靶点。将被研究的初始系统包括与帕金森氏症和癌症相关的蛋白质。预计了解这些蛋白质的结构和影响其结构的因素将极大地促进药物开发和最终的治疗。

DESCRIPTION (provided by applicant): Protein structure is directly connected to proper cellular function and offers a molecular level understanding of the biochemical pathways related to health or disease. This project will develop a method for examining protein structure in the gas phase. This will be accomplished by modifying a state of the art mass spectrometer with a tunable UV laser capable of generating novel protein radicals. Observation of the dissociation patterns of these radical proteins will reveal a series of distance constraints that can be leveraged into three dimensional structures with the aid of molecular dynamics simulations. This method will allow the advantages of speed, sensitivity, and flexibility which are highly optimized for the mass spectrometric analysis of proteins to be applied to the challenging area of structure determination. Therefore, many target proteins which would be intractable for traditional methods will now be viable targets for structure elucidation. Initial systems that will be investigated include proteins that are related to Parkinson's disease and cancer. It is anticipated that knowledge of the structures of these proteins and factors that influence their structures will greatly facilitate drug development and eventual treatments.