Ultrahigh Throughput Deep UV Raman Spectrometer for Probing Protein Structure

用于探测蛋白质结构的超高通量深紫外拉曼光谱仪

• 批准号: 7880179
• 负责人: SANFORD A. ASHER
• 金额: $ 26.7万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7880179
• 关键词: Amides; Biological; Dependence; Development; Enzymatic Biochemistry; Equilibrium; Free Energy; Frequencies; Health; Human; Individual; Investigation; Kinetics; Lasers; Length; Light; Measurement; Methodology; Methods; Molecular; Molecular Conformation; Molecular Structure; Monitor; Morphologic artifacts; Noise; Optics; Peptides; Process; Protein Dynamics; Proteins; Raman Spectrum Analysis; Reaction; Signal Transduction; Silicon Dioxide; Source; Spectrum Analysis; Structure; Technology; Ultraviolet Rays; Work; design; human disease; improved; insight; instrument; instrumentation; light scattering; novel; photonics; protein folding; protein structure; public health relevance

DESCRIPTION (provided by applicant): Recent advances in UV resonance Raman spectroscopy have demonstrated its unique power to examine biomolecular structure and dynamics. The spectra are very sensitive to molecular geometry due to the dependence of the normal mode frequencies on bond lengths and bond angles. The UV Raman spectra detail both static and dynamic structural changes. The information content of UVRR spectroscopy is presently limited by spectrometer throughput, since modern deep UV laser sources provide higher powers than can be utilized for resonance Raman excitation. The excitation intensity threshold is limited by the onset of nonlinear optical processes. We will develop a novel deep UV Raman spectrometer with dramatically improved sensitivity and signal-to-noise ratios to enable incisive investigations of biological structure and function. This spectrometer will be targeted for determining protein and peptide secondary structure and for kinetic studies which examine the dynamics of protein folding. The work proposed here will revolutionize UVRR measurements by developing a new spectrometer which will collect much more Raman scattered light than previous instruments. PUBLIC HEALTH RELEVANCE: Major advances in the understanding of biomolecular structure and function result from the development of more incisive methods to visualize molecular structure and dynamics. An increased understanding of biomolecular structure and function directly leads to insight into human health and is essential for developing methods to treat human disease. The resulting more powerful UV Raman instrumentation will give new insights into the mechanism(s) of protein folding, which is arguably the most important outstanding problem in enzymology.

描述（由申请人提供）：紫外共振拉曼光谱学的最新进展已经证明了其检查生物分子结构和动力学的独特能力。光谱是非常敏感的分子的几何形状，由于依赖的正常模式的频率上的键长和键角。UV拉曼光谱详细描述了静态和动态结构变化。UVRR光谱的信息内容目前受到光谱仪吞吐量的限制，因为现代深UV激光源提供比可用于共振拉曼激发的功率更高的功率。激发强度阈值受到非线性光学过程的起始的限制。我们将开发一种新型的深紫外拉曼光谱仪，具有显着提高的灵敏度和信噪比，使生物结构和功能的深入调查。该光谱仪将用于确定蛋白质和肽的二级结构，并用于研究蛋白质折叠动力学的动力学研究。这里提出的工作将彻底改变UVRR测量通过开发一种新的光谱仪，它将收集更多的拉曼散射光比以前的仪器。公共卫生相关性：对生物分子结构和功能的理解的主要进展来自于更敏锐的分子结构和动力学可视化方法的发展。增加对生物分子结构和功能的理解直接导致对人类健康的洞察，并且对于开发治疗人类疾病的方法至关重要。由此产生的更强大的紫外拉曼仪器将提供新的见解的机制（S）的蛋白质折叠，这可以说是最重要的突出问题，在酶学。