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）：蛋白质结构直接连接到适当的细胞功能，并提供了对与健康或疾病有关的生化途径的分子水平。该项目将开发一种在气相中检查蛋白质结构的方法。这将通过用可调的紫外线激光器能够产生新型蛋白质自由基来修饰最先进的质谱仪的状态来实现。观察这些自由基蛋白的解离模式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将其利用为三维结构。此方法将允许速度，灵敏度和灵活性的优势，这些优化对于蛋白质的质谱分析非常优化，可以应用于结构确定的具有挑战性领域。因此，对于传统方法而言，许多目标蛋白现在将成为结构阐明的可行靶标。将要研究的初始系统包括与帕金森氏病和癌症有关的蛋白质。可以预料，这些蛋白质的结构和影响其结构的因素的知识将极大地促进药物开发和最终治疗。