Cracking the chemical shift code

点击翻译按钮获取中文摘要

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.