A high field NMR facility at Dundee for structural and interaction studies.

邓迪的高场核磁共振设施用于结构和相互作用研究。

• 批准号: BB/F011636/1
• 负责人: Frank Sargent
• 金额: $ 22.41万
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF011636%2F1
• 关键词: field; NMR; facility; Dundee; structural

All matter consists of atoms and at the nucleus of every atom are protons and neutrons. Nuclei that contain an odd number of protons or neutrons are magnetic. Nuclear Magnetic Resonance (NMR) spectroscopy uses very powerful magnetic fields and pulses of radio waves to exploit the magnetic properties of 'odd-numbered nuclei' such as 1H (hydrogen atom or proton), 15N (nitrogen), 13C (carbon), 19F (fluorine) and 31P (phosphorus). Using this technique it is possible for scientists to identify almost every different atom in a protein, nucleic acid, or small drug molecule. This can be very useful, for example, in building up a picture of the 3-dimensional structure of one of these molecules. At Dundee University NMR spectroscopy has been used to determine the structures of nucleic acids and some proteins. The possible uses for NMR spectroscopy are much more varied, however. It is possible to determine the overall size of a protein or complex of proteins, for example, and it is possible to detect which particular atoms of a protein or other molecule undergo a change in local environment when another protein or molecule interacts with it. When proteins 'talk' to each other in the cell they very often physically interact, and NMR can therefore help scientists identify interacting partners. NMR has proven to be immensely useful in drug discovery by identifying small molecules that bind to target 'receptors' of medical interest. In this application nine scientists from the College of Life Sciences outline their ideas for using a new NMR instrument to enhance their research. There are four broad topics under investigation: 1. Bacterial protein transport 2. Nucleic acid structure and folding 3. NMR in drug development 4. Protein modification and its role in gene regulation All of these already well-funded and world-class research projects propose to use NMR spectroscopy to determine structures and/or to assess interactions between molecules. The need for an upgraded NMR spectrometer at Dundee is very great. In recent years the College has expanded its structural biology, molecular microbiology, and drug discovery programs. The machine with the largest magnet in Dundee ('11.744 Tesla' or '500 MHz' spectrometer) is 18 years old and requires upgrading. The College of Life Sciences has commissioned a central suite of smaller NMR and Magnetic Resonance Imaging (MRI) spectrometers within the new Sir James Black Centre. It is proposed here to upgrade the existing 500 MHz spectrometer (at a fraction of the cost of buying a brand new instrument) and to house it in the central 'Nuclear Magnetic Resonance Spectroscopy and Imaging Facility'. The quality of the researchers and research outlined in this proposal, coupled with the versatility, sensitivity, and cost-effectiveness of the upgraded spectrometer requested, will promote increased local, national and international collaborations between scientists, attract a constant stream of new research funding, result in high quality research publications, novel structures and pharmaceuticals, as well as teaching and training future generations of NMR experts.

一切物质都由原子组成，每个原子的原子核上都有质子和中子。含有奇数个质子或中子的原子核是磁性的。核磁共振（NMR）光谱学使用非常强大的磁场和无线电波脉冲来利用“奇数核”的磁性，如1H（氢原子或质子）、15N（氮）、13C（碳）、19F（氟）和31P（磷）。利用这项技术，科学家们有可能识别蛋白质、核酸或小药物分子中几乎每一个不同的原子。这是非常有用的，例如，在建立这些分子的三维结构图时。在邓迪大学，核磁共振光谱已经被用来确定核酸和一些蛋白质的结构。然而，核磁共振光谱学的可能用途要多样得多。例如，它可以确定蛋白质或蛋白质复合物的总体大小，并且可以检测到当另一种蛋白质或分子与之相互作用时，蛋白质或其他分子的哪些特定原子在局部环境中发生变化。当蛋白质在细胞中相互“交谈”时，它们经常发生物理相互作用，因此核磁共振可以帮助科学家识别相互作用的伙伴。核磁共振已被证明在药物发现中非常有用，它可以识别与医学兴趣目标“受体”结合的小分子。在这个应用程序中，来自生命科学学院的九位科学家概述了他们使用一种新的核磁共振仪器来加强他们研究的想法。正在调查的有四个主要主题：1。细菌蛋白转运2。核酸结构与折叠核磁共振在药物开发中的应用蛋白质修饰及其在基因调控中的作用所有这些已经资金充足和世界级的研究项目都建议使用核磁共振波谱来确定结构和/或评估分子之间的相互作用。邓迪对升级核磁共振光谱仪的需求非常大。近年来，学院扩大了结构生物学、分子微生物学和药物发现项目。拥有邓迪最大磁体（“11.744特斯拉”或“500 MHz”光谱仪）的机器已经使用了18年，需要升级。生命科学学院委托在新的詹姆斯·布莱克爵士中心安装一套小型核磁共振和磁共振成像（MRI）光谱仪。这里建议升级现有的500兆赫光谱仪（只需要购买全新仪器的一小部分费用），并将其安置在中央“核磁共振光谱和成像设施”中。本提案中概述的研究人员和研究质量，加上所要求的升级光谱仪的多功能性，灵敏度和成本效益，将促进当地，国家和国际科学家之间的合作，吸引源源不断的新研究资金，产生高质量的研究出版物，新结构和药物，以及教学和培训未来几代核磁共振专家。