Enabling new characterisation methods for dynamic systems through the upgrade of 700 MHz solution NMR spectrometer

沃里克大学的高场700 MHz溶液NMR光谱仪是在2004-2005年期间安装的。从那时起，它支持了大量主要由BBSRC和其他UKRI理事会资助的研究项目，在Nature，Nature Chemistry和Nature Chemical Biology等期刊上发表了许多高影响力的跨学科论文。它还在培养下一代核磁共振专家方面发挥了关键作用，我们的许多研究生/PDRA从使用该仪器中受益匪浅。该仪器是生物分子溶液NMR研究活动的核心，通过多学科合作网络在沃里克大学内跨部门，以及支持沃里克以外的高调合作。然而，经过十多年的大量使用，它现在已经超过了其生命周期的终止时间，Avance II控制台和旧的TCI冷冻探针已经完全过时，导致频繁的故障，延长的停机时间和有限的能力。更重要的是，自从光谱仪安装以来，控制台设计和冷冻探针技术都取得了巨大进步，这使得广泛的新功能强大的技术成为可能，而这是旧一代仪器无法实现的。在本提案中，我们申请资金更新700 MHz溶液NMR系统，将老化的控制台升级为Avance NEO，并购买新的冷冻探针、TXO和TCI，这将扩大我们的核磁共振能力，使生物核磁共振光谱学的尖端能力，以支持大量的既定和早期职业研究人员（>20 PI及其研究小组）参与了广泛的国际领先的研究。拟议的升级是最紧迫的，以避免对沃里克一个成熟和非常成功的研究领域产生负面影响。新的TCI探针将大大提高溶解在高离子强度生理溶液中的样品的灵敏度，并支持从小分子、生物活性天然产物到蛋白质的发现。它还将为氟光谱学和相关的最先进实验提供新的能力，以表征生物分子系统（例如蛋白质-聚糖系统和大蛋白质复合物）的相互作用、构象动力学和结构。TXO探针的加入将为先进的大型动态蛋白质工作带来新的尖端能力，这将巩固我们在基因组指导的生物活性天然产物发现和生物合成酶的集成结构生物学等领域的国际领先地位。英国的地方和国家NMR社区也可以从这次升级中受益，我们已经与米德兰的同事协调了我们的应用程序，以确保新获得的能力与该地区的现有设施互补。我们还提议通过透明的同行评审流程和与UKRI资助的ConnectNMR网络集成的访问机制，向英国NMR社区提供高达15%的仪器时间。

The high field 700 MHz solution NMR spectrometer at the University of Warwick was installed during 2004-2005. Since then it has supported large number of research projects mainly funded by the BBSRC and other UKRI councils, led to numerous high-impact interdisciplinary publications in journals such as Nature, Nature Chemistry and Nature Chemical Biology. It has also played a pivotal role in training up the next generation of NMR specialists, many of our research students/PDRAs have benefited enormously from accessing to this instrument. The instrument is central to biomolecular solution NMR research activities, across departments within the University of Warwick via multidisciplinary collaborative networks, as well as supporting high-profile collaborations outside Warwick. However, after more than a decade of heavily usage, it is now >5 years beyond its end-of-life cycle, the Avance II console and the old TCI cryoprobe are completely obsolete, resulting in frequent malfunctions, extended downtime and limited capabilities. More importantly, since the spectrometer's installation, huge advances have been made both in the console design and cryoprobe technology, which enable a wide range of new powerful techniques and are not possible with the old-generation of instrumentation.In this proposal, we request funds to renew the 700 MHz solution NMR system by upgrading the aging console to Avance NEO and purchasing new cryoprobes, TXO and TCI, which will expand our NMR capacity and enable cutting-edge capabilities in biological NMR spectroscopy, to support large number of both established and early-career research staff (>20 PIs and their research groups) involved in a wide range of internationally leading research. The proposed upgrade is of utmost urgency to avoid negatively impacting on a well established and very successful field of research at Warwick. The new TCI probe will deliver substantial improvements in sensitivity for samples dissolved in high ionic strength physiological solutions and supporting work from small molecule, bioactive natural products discovery to proteins. It will also provide new capabilities for fluorine spectroscopy and related state-of-the-art experiments for characterising interactions, conformational dynamics and structures of biomolecular systems (e.g. protein-glycan systems and large protein complexes). The addition of a TXO probe will additionally bring new cutting-edge capabilities for advanced large and dynamic protein-based work, which will fortify our internationally leading position in field such as genome guided bioactive natural product discovery and integrated structural biology of biosynthetic enzymes. Both local and national NMR communities in the UK can also benefit from this upgrade, we have co-ordinated our application with colleagues in the Midland to ensure that newly gained capabilities are complementary with existing facilities in the region. We also proposed to offer up to 15% of the instrument time to the UK NMR communities through a transparent peer-review process and access mechanism integrated with the UKRI funded ConnectNMR network.