Realising the potential of cryogenic magic-angle spinning nuclear magnetic resonance

新药物和新材料的发展需要了解分子结构，即分子内原子的精确排列。例如，如果一个人知道一个有故障的蛋白质分子的确切形状，他可以尝试设计其他与之结合的分子，以防止它造成太大的损害。科学家只有几种方法可以用来了解蛋白质等大分子的结构。最成功的方法是X射线结晶学。然而，这种强大的方法需要晶体，而晶体很难制造出许多非常重要的生物分子，特别是位于细胞膜(膜蛋白)中的受体蛋白质类型。另一种有前途的方法被称为固态核磁共振(核磁共振)，它利用了氢、碳和氮原子中心的许多原子核都是弱磁性的事实，表现为小磁棒的行为。在核磁共振中，无线电波与强磁场一起使用来探测这些磁铁之间的相互作用，使人们能够建立分子结构的图像。固体核磁共振已经被用来从膜蛋白等大的生物分子中获得结构信息，而不需要形成晶体。不幸的是，核磁共振信号非常弱。通常需要相当大量的样品。这极大地限制了这种方法的应用，因为许多最有趣和最重要的分子只有很少的数量。在目前的项目中，我们设计和建造了在非常低的温度下进行固态核磁共振的设备，接近液体氦的沸点(4.2开尔文，或-269摄氏度)。在这些温度下，核磁共振信号要强得多。这将使生物学家和化学家能够用比以前少10倍的样品来获得重要的分子结构信息。该项目在技术上要求很高，因为人们不仅要使样品保持非常低的温度，还必须使其以与所施加的磁场成一定角度快速旋转(这被称为魔角旋转，或MAS)。这种快速的样品旋转对于获得最具信息量的核磁共振信号是必要的。低温魔角旋转核磁共振是一项重大的技术挑战，我们的项目结合了样品纺丝、电子学和低温方面的领先专业知识，以克服这些困难。在翻译助学金中，我们将进一步开发设备，以便快速方便地交换样品。我们还将邀请外部用户在我们的设备上运行他们的样品，以便在英国国内和国际上发展和加强科学合作。我们将对南安普敦和利兹生产的两套不同的生物分子进行实验，以阐明它们的分子结构和作用机制。我们还将研究具有重大技术价值的导电材料，如有机导体、半导体和超导体。低温MAS-核磁共振实验将能够以亚分子分辨率可视化电子传导性质。这将极大地帮助开发应用于计算、通信、太阳能和燃料电池的新材料。

Progress in the development of new medicines and materials requires knowledge of molecular structures, i.e. the precise arrangment of atoms within molecules. For example, if one knows the precise shape of a malfunctioning protein molecule, one can try to design other molecules which bind to it, so as to prevent it from doing too much damage. Scientists only have a few methods available for finding out about the structures of large molecules like proteins. The most successful method is X-ray crystallography. However, this powerful method requires crystals, which are difficult to produce for many very important biomolecules, especially the type of receptor proteins which sit inside cell membranes ( membrane proteins ).Another promising method is called solid-state NMR (nuclear magnetic resonance), which uses the fact that many of the nuclei at the centres of hydrogen, carbon and nitrogen atoms are weakly magnetic, and behave as small bar magnets. In NMR, radiowaves are used together with a strong magnetic field to probe the interactions between these magnets, allowing one to build up a picture of the molecular structure. Solid-state NMR has been used to obtain structural information from large biomolecules such as membrane proteins, without the need to form crystals. Unfortunately, the NMR signals are very weak. Rather large amounts of sample are often required. This greatly limits the application of this method, since many of the most interesting and important molecules are only available in very small quantities. In the current project we have designed and constructed equipment to perform solid-state NMR at very low temperatures, approaching the boiling point of liquid Helium (4.2 Kelvin, or -269 degrees C). The NMR signal is much stronger at these temperatures. This will allow biologists and chemists to obtain the vital molecular structural information using at least 10 times less sample than was possible before. The project is technically demanding because one must not only keep the sample very cold, but also rotate it very rapidly at a certain angle to the applied magnetic field (this is called magic-angle-spinning, or MAS). This rapid sample rotation is necessary to obtain the most informative NMR signals. Cryogenic magic-angle-spinning NMR is a major technical challenge, and our project combines leading expertise in sample spinning, electronics and cryogenics, in order to overcome these difficulties. In the translation grant we will develop the equipment further so as to allow the samples to be exchanged rapidly and conveniently. We will also invite external users to run their samples on our equipment, in order to develop and strengthen scientific collaborations both within the UK and internationally. We will perform experiments on two different sets of biomolecules produced in Southampton and Leeds, in order to elucidate their molecular structure and functional mechanism. We will also study conducting materials of great technological importance, such as organic conductors, semiconductors and superconductors. The cryoMAS-NMR experiments will allow visualization of the electronic conduction properties with sub-molecular resolution. This will greatly assist the development of new materials with applications in computing, communications, solar energy, and fuel cells.