Acquisition of a 500 MHz NMR Console

描述(申请人提供)：虽然蛋白质的结构具有唯一性和稳定性是至关重要的，但这种结构的变化对于结合和催化是必不可少的。现在很明显，许多蛋白质识别过程将构象变化作为功能的必备事件。通过这种方式，蛋白质的结构和动力学通过大尺度和小尺度的构象波动与生物活性密切相关。加州大学圣迭戈分校化学和生物化学系Jennings、Opella、Taylor、Handel和Komives实验室的研究工作总体上旨在了解蛋白质和多肽折叠的动力学、分子识别和与功能调节相关的构象开关。我们每个研究项目中的一个关键要素是使用高分辨率核磁共振方法来阐明结构、探索蛋白质/配体识别机制、了解折叠反应和表征天然多肽/蛋白质动力学。我们每个实验室研究进展的一个主要障碍是，获取部门仪器的途径受到对光谱仪时间的高要求的限制。目前，部级生物分子核磁共振波谱仪的典型等待时间为2个半月至3个月。我们正在申请资金，为我们的500 MHz瓦里安联合核磁共振光谱仪购买一个现代化的控制台。有了新的控制台，该光谱仪将能够进行全方位的多维核磁共振实验，以研究同位素标记的多肽和蛋白质。用具有全PFG功能的新控制台取代单独的控制台，并为仪器配备三谐振三轴梯度探头，将大大加强我们每个实验室和部门的研究工作，因为它允许实施和开发现代脉冲序列，并为要求苛刻的应用提供更高的灵敏度，例如分析边缘可溶的蛋白质和多肽。

DESCRIPTION (provided by applicant): While it is critical for a protein's structure to be unique and stable, changes in this structure are imperative for binding and catalysis. It is now evident that many protein recognition processes incorporate conformational changes as a requisite event for function. In this manner, protein structure and dynamics are intimately linked with biological activity via both large and small scale conformational fluctuations. Research efforts in the Jennings, Opella, Taylor, Handel, and Komives laboratories in the Department of Chemistry and Biochemistry at UCSD are directed, in general towards understanding the dynamics of protein and peptide folding, molecular recognition and the conformational switches that correlate the regulation of function. A key element in each of our research programs is the use of high-resolution NMR methods for structure elucidation, probing protein/ligand recognition mechanisms, understanding folding reactions and characterizing native peptide/protein dynamics. A major impediment to research progress in each of our laboratories is the fact that access to departmental instruments is restricted by the high demand of spectrometer time. Currently, the typical waiting time on the departmental biomolecular NMR spectrometers is 2 1/2 - 3 months. We are requesting funds for the purchase of a modern console for our 500 MHz Varian Unity NMR spectrometer. With a new console, the spectrometer will be capable of the full range of multidimensional NMR experiments for studies of isotopically labeled peptides and proteins. The replacement of solely the console with a new console with full PFG capabilities and equipping the instrument with a triple-resonance triple axis gradient probe will significantly enhance research efforts in each of our laboratories and the Department by allowing implementation and development of modern pulse sequences as well as affording enhanced sensitivity for demanding applications such as analysis of marginally soluble proteins and peptides.