NMR Cryoprobe for Structural Biology Research

描述（由申请人提供）：本申请申请资金用于购买冷冻探针，以大幅提高西北大学WCAS结构生物学核磁共振设施中高分辨率600 MHz核磁共振仪器的灵敏度。在之前NIH和NSF的支持下，西北大学的结构生物学家建立了一个大分子核磁共振资源，并取得了显著的成果。600兆赫光谱仪是该设施中唯一的核磁共振仪器，被大量连续使用。与传统的第三代探针相比，冷冻探针提供的灵敏度增加了2到3倍，这意味着采集时间减少了4到9倍，从而显着提高了吞吐量。因此，获得冷冻探针将更有效地满足目前使用该仪器的多达六个研究小组日益增长的科学需求。它也是一种具有成本效益的解决方案，因为新的600 MHz仪器的购置成本明显高于冷冻探头。低温探针灵敏度提高的另一个好处是降低了样品浓度要求。因此，对生产成本高、容易高浓度聚集或化学性质不稳定的样品的研究很容易得到促进，从而为研究以前这种技术无法解决的问题提供了可能。我们提议获得的冷冻探针将具有第三代大分子核磁共振探针的所有功能，包括优化的1H频率直接检测，在1H， 2H， 13C和15N频率同时照射，以及主动屏蔽z轴梯度。探头的低温冷却需要一个闭式循环低温系统，包括氦气冰箱，温度控制器，氦气压缩机，涡轮真空泵以及冷水机组作为基本配件。低温系统和冷水机与核磁共振设施的当前布局完全兼容，并且可以很容易地适应，只需对设施进行微小的修改。场地平面图已经得到了制造商的批准。低温探针连同闭式循环低温系统和冷水机作为附件将重建WCAS设施中的600 MHz仪器，使其成为最先进的大分子核磁共振资源。

DESCRIPTION (provided by applicant): This proposal requests funds for the acquisition of a cryoprobe for substantially increasing the sensitivity of the high-resolution 600 MHz NMR instrument in the WCAS Structural Biology NMR Facility at Northwestern University. With previous NIH and NSF support, Northwestern structural biologists established a resource for macromolecular NMR that has yielded significant results. The 600 MHz spectrometer, which is the only NMR instrument in the facility, is used heavily and continuously. The two- to three-fold increase in sensitivity afforded by cryoprobes over conventional third generation probes translates into four- to nine-fold reduction in acquisition times, thereby significantly enhancing throughput. The acquisition of a cryoprobe will thus more effectively meet the growing scientific needs of as many as six research groups that currently use the instrument. It also represents a cost-effective solution since the acquisition costs of a new 600 MHz instrument is significantly higher than that of a cryoprobe. An added benefit of the increased sensitivity of the cryoprobe is the lowered sample concentration requirements. Thus, studies of samples that are expensive to produce, prone to aggregate at high concentrations, or are otherwise chemically unstable are readily facilitated, thus opening up the possibility of studying research problems previously inaccessible by this technique. The cryoprobe we propose to acquire will have all the capabilities of third generation probes for macromolecular NMR including optimized direct detection of 1H frequencies, simultaneous irradiation at 1H, 2H, 13C, and 15N frequencies, and actively shielded z-axis gradient. Cryogenic cooling of the probe requires a closed-cycle cryogenic system comprising a helium refrigerator, a temperature controller, a helium compressor, and a turbo vacuum pump as well as a water chiller unit as essential accessories. The cryogenic system and the water chiller are fully compatible with and can be readily accommodated in the current layout of the NMR facility with only minor modifications to the facility. Approval of the site plan has been already obtained from the manufacturer. The cryoprobe along with the closed-cycle cryogenic system and water chiller as accessories will thus reestablish the 600 MHz instrument in the WCAS facility as a state-of-the-art resource for macromolecular NMR.