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）：紫外线共振拉曼光谱法的最新进展证明了其独特的功能，可以检查生物分子结构和动力学。由于正常模式频率对键长和键角的依赖性，光谱对分子几何形状非常敏感。紫外线拉曼光谱详细介绍了静态和动态结构变化。 UVRR光谱的信息含量目前受到光谱仪吞吐量的限制，因为现代的深紫外线激光源提供的功率比可用于共振拉曼激发的能力更高。激发强度阈值受非线性光学过程的开始限制。我们将开发一种新型的深紫外拉曼光谱仪，具有显着提高灵敏度和信噪比的比例，以敏锐地研究生物结构和功能。该光谱仪将针对确定蛋白质和肽二级结构以及研究蛋白质折叠动力学的动力学研究。这里提出的工作将通过开发一个新的光谱仪来彻底改变UVRR测量，该光谱仪将收集比以前的乐器更多的拉曼分散光。公共卫生相关性：理解生物分子结构和功能的重大进展是由于开发更敏锐的方法来可视化分子结构和动力学。对生物分子结构和功能的越来越多的理解直接导致人们对人类健康的了解，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线拉曼仪器将为蛋白质折叠的机制提供新的见解，这可以说是酶学中最重要的杰出问题。