Ultrahigh Throughput Deep UV Raman Spectrometer for Probing Protein Structure

描述（由申请人提供）：紫外共振拉曼光谱的最新进展已经证明了它在检查生物分子结构和动力学方面的独特力量。由于键长和键角依赖于正模频率，光谱对分子几何结构非常敏感。紫外拉曼光谱详细描述了静态和动态结构变化。由于现代深紫外激光源提供比共振拉曼激发更高的功率，UVRR光谱的信息内容目前受到光谱仪吞吐量的限制。非线性光学过程的发生限制了激发强度阈值。我们将开发一种新型的深紫外拉曼光谱仪，其灵敏度和信噪比大大提高，能够深入研究生物结构和功能。该光谱仪将用于确定蛋白质和肽的二级结构以及用于检查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种新的光谱仪来彻底改变UVRR测量，该光谱仪将比以前的仪器收集更多的拉曼散射光。公共卫生相关性：对生物分子结构和功能的理解取得了重大进展，这是由于开发了更深刻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进一步了解直接导致对人类健康的洞察，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为蛋白质折叠机制提供新的见解，这可以说是酶学中最重要的突出问题。

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.