Cracking the chemical shift code

破解化学位移密码

• 批准号: 195727-2009
• 负责人: Wishart, David
• 金额: $ 2.91万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=497901
• 关键词: Cracking; chemical; shift; code

Nuclear Magnetic Resonance (NMR) spectroscopy is one of the most powerful analytical techniques available for characterizing chemical compounds. It is routinely used in academic and industrial labs around the world to help chemists identify the molecules they have made or isolated. Specifically, NMR is a spectroscopic technique that allows scientists to detect radio frequencies that are emitted when atoms are exposed to very strong magnetic fields. Just as different AM or FM radio stations transmit their broadcast signals at different frequencies, different types of atoms will emit their radio waves at specific frequencies too. These characteristic "broadcast" frequencies are called chemical shifts. Chemical shifts are often used by NMR spectroscopists as specific markers to identify the type of atom in a given chemical compound. It has been known for a long time that chemical shifts can also provide information about the type, location. local geometry and even the motion of atoms relative to other atoms in a molecule. However, deciphering this information from raw chemical shift data is quite difficult, especially for large molecules such as peptides and proteins. Recently, my laboratory has made some exciting progress in "decoding" the structural and dynamic information that can be measured from protein chemical shifts. We want to extend this work and to see if we can apply this knowledge to more rapidly and accurately determine the 3D structure and dynamics of proteins using only chemical shift information. With conventional methods, it typically takes very skilled NMR spectroscopists more than six months of painstaking, manually intensive work to assign, generate and refine a protein structure. We believe that our new, chemical shift-based approach could potentially shorten this time from six months to as little as six minutes. This novel approach could also open up the possibility of characterizing proteins and protein complexes that are too difficult or too large to study by conventional NMR. Such an improvement in speed and accuracy could have profound implications in the application of NMR to biology, chemistry and pharmaceutical research.

核磁共振（NMR）光谱是可用于表征化学化合物的最强大的分析技术之一。 它通常在世界各地的学术和工业实验室中使用，以帮助化学家识别他们制造或隔离的分子。 具体而言，NMR是一种光谱技术，它允许科学家检测原子暴露于非常强的磁场时发出的无线电频率。 就像不同的AM或FM广播电台以不同的频率传输其广播信号一样，不同类型的原子也会以特定的频率发射无线电波。 这些特征性的“广播”频率称为化学位移。 NMR光谱学家通常将化学位移用作特定标记，以识别给定化合物中原子的类型。 很长一段时间以来，化学移位也可以提供有关位置类型的信息。局部几何形状，甚至原子相对于分子中其他原子的运动。 但是，从原始化学移位数据中解密这些信息非常困难，尤其是对于大分子（例如肽和蛋白质）。最近，我的实验室在“解码”可以从蛋白质化学转移中测量的结构和动态信息方面取得了令人兴奋的进步。 我们希望扩展这项工作，看看是否可以将这些知识应用于仅使用化学移位信息的3D结构和蛋白质动态的更快，准确地确定。使用常规的方法，通常需要非常熟练的NMR光谱学家进行六个月以上的艰苦，手动密集的工作来分配，生成和完善蛋白质结构。 我们认为，我们的新的，基于化学转移的方法可能会从六个月缩短到六分钟。 这种新颖的方法还可以打开表征蛋白质和蛋白质复合物的可能性，这些蛋白质和蛋白质复合物太困难或太大而无法通过常规NMR进行研究。 这种速度和准确性的这种提高可能对NMR在生物学，化学和药物研究中的应用具有深远的影响。