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

• 批准号: 8319335
• 负责人: Ryan Roy Julian
• 金额: $ 18万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8319335
• 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

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，并提供了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。这将通过用能够产生新型蛋白质自由基的可调谐UV激光器修改现有技术的质谱仪来实现。这些自由基蛋白质的解离模式的观察将揭示一系列的距离约束，可以利用到三维结构的分子动力学模拟的帮助下。这种方法将允许速度，灵敏度和灵活性的优点，这是高度优化的蛋白质的质谱分析，以应用于结构测定的挑战性领域。因此，许多传统方法难以处理的靶蛋白质现在将成为结构解析的可行靶标。将被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治疗。