Cracking the chemical shift code

核磁共振（NMR）光谱是表征化合物的最强大的分析技术之一。 它通常用于世界各地的学术和工业实验室，以帮助化学家识别他们制造或分离的分子。 具体来说，NMR是一种光谱技术，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发射广播信号一样，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”频率被称为化学位移。 化学位移通常被NMR光谱学家用作特定标记，以识别给定化合物中的原子类型。 很久以前就知道化学位移也可以提供关于类型、位置的信息。局部几何甚至分子中原子相对于其他原子的运动。 然而，从原始化学位移数据中破译这些信息是相当困难的，特别是对于大分子，如肽和蛋白质。最近，我的实验室在“解码”可以从蛋白质化学位移测量的结构和动力学信息方面取得了一些令人兴奋的进展。 我们希望扩展这项工作，看看我们是否可以应用这些知识，仅使用化学位移信息更快速，更准确地确定蛋白质的3D结构和动力学。使用传统方法，通常需要非常熟练的NMR光谱仪超过六个月的艰苦，手动密集的工作来分配，生成和改进蛋白质结构。 我们相信，我们新的基于化学位移的方法可能会将这一时间从六个月缩短到六分钟。 这种新方法还可以开辟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提高可能对NMR在生物学，化学和药物研究中的应用产生深远的影响。

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.