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

通过质量数快速测定超灵敏三维蛋白质结构

基本信息

批准号：
8510672
负责人：
Ryan Roy Julian
金额：
$ 21.05万
依托单位：
UNIVERSITY OF CALIFORNIA RIVERSIDE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-15 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8510672
关键词：
Actins Area Biochemical Pathway Biological Process Biology Cell physiology Cells Charge Chemistry Coin Complex Coupled Development Diagnosis Disease Dissociation Dyes Evaluation Fourier transform ion cyclotron resonance Future Gases Goals Health Human Human body Ions Knowledge Lasers Ligands Macrolides Malignant Neoplasms Mass Spectrum Analysis Methodology Methods Molecular Molecular Chaperones Nature Optics Parkinson Disease Pattern Performance Phase Photochemistry Probability Protein Analysis Proteins Resolution Series Speed Structure System Techniques Testing Toxin Ubiquitin Vacuum base cytochrome c data acquisition design drug development flexibility human MAP3K1 protein human disease inhibitor/antagonist ion mobility mass spectrometer molecular dynamics nervous system disorder novel protein structure research study response synuclein three dimensional structure

项目摘要

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.

描述（由申请人提供）：蛋白质结构与适当的细胞功能直接相关，并提供对与健康或疾病相关的生化途径的分子水平理解。该项目将开发一种在气相中检查蛋白质结构的方法。这将通过修改最先进的质谱仪和能够产生新型蛋白质自由基的可调谐紫外激光器来实现。对这些自由基蛋白解离模式的观察将揭示一系列距离约束，这些距离约束可以借助分子动力学模拟用于三维结构。该方法将具有速度、灵敏度和灵活性的优点，这些优点针对蛋白质的质谱分析进行了高度优化，可应用于具有挑战性的结构测定领域。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可行靶标。将研究的初始系统包括与帕金森病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。