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表明，它在检测生物分子结构和动力学方面具有独特的能力。由于简正模式频率与键长和键角的关系，光谱对分子几何非常敏感。紫外拉曼光谱详细描述了静态和动态的结构变化。UVRR光谱的信息量目前受到光谱仪吞吐量的限制，因为现代深紫外激光光源提供的功率比共振拉曼激发所能利用的更高。激发强度阈值受非线性光学过程的影响。我们将开发一种新型的深紫外拉曼光谱仪，大大提高灵敏度和信噪比，使深入研究生物结构和功能成为可能。该光谱仪将用于确定蛋白质和多肽的二级结构，并用于研究蛋白质折叠的动力学。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。与公众健康相关：在理解生物分子结构和功能方面的重大进展源于更深入的方法的发展，以可视化分子结构和动力学。增加对生物分子结构和功能的了解直接导致对人类健康的洞察，并对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的机制(S)提供新的见解，蛋白质折叠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.