NMR Cryoprobe for Structural Biology Research

描述(由申请人提供)：该提案申请资金用于购买冷冻探头，以显著提高西北大学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，西北结构生物学家建立了一个大分子核磁共振资源，并取得了重大成果。600 MHz光谱仪是该设施中唯一的核磁共振仪器，频繁而连续地使用。与传统的第三代探头相比，低温探头的灵敏度提高了两到三倍，这意味着采集时间减少了四到九倍，从而显著提高了吞吐量。因此，获得低温探头将更有效地满足目前使用该仪器的多达6个研究小组日益增长的科学需求。这也是一种具有成本效益的解决方案，因为一台新的600兆赫仪器的购置成本比低温探头高得多。低温探头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、容易在高浓度下聚集或在其他方面化学不稳定的样品的研究很容易被促进，从而打开了研究以前无法通过该技术获得的研究问题的可能性。我们计划获得的低温探针将具有第三代大分子核磁共振探针的所有能力，包括优化的1H频率直接检测，1H、2H、13C和15N频率的同时照射，以及主动屏蔽的z轴梯度。探测器的低温冷却需要一个闭合循环低温系统，该系统包括一个氦制冷机、一个温度控制器、一个氦压缩机、一个涡轮真空泵以及一个冷水机组作为基本附件。低温系统和冷水机与核磁共振设施的当前布局完全兼容，只需对设施进行微小的修改，就可以很容易地适应。场地平面图已获得制造商的批准。因此，低温探头连同闭合循环低温系统和冷水器作为附件，将重建WCAS设施中的600 MHz仪器，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.