Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Biochemistry. 2021 Nov 23;60(46):3452-3454. doi: 10.1021/acs.biochem.1c00141. Epub 2021 Mar 30.
The study of protein dynamics using the measurement of relaxation times by NMR was based on a set of studies in the mid-20th century that outlined theories and methods. However, the complexity of protein NMR was such that these simple experiments were not practical for application to proteins. The advent of techniques in the 1980s for isotopic labeling of proteins meant that pulse sequences could now be applied in multidimensional NMR experiments to enable per-residue information about the local relaxation times. One of the earliest advances was published in in 1989. The paper "Backbone dynamics of proteins as studied by N inverse detected heteronuclear NMR spectroscopy: application to staphylococcal nuclease" by Lewis Kay, Dennis Torchia, and Ad Bax delineated a set of pulse sequences that are used with minor modifications even today. This paper, with others from a limited number of other laboratories, forms the basis for the experimental determination of the backbone dynamics of proteins. The biological insights obtained from such measurements have only increased in the past 30 years. Sometimes, the best and perhaps only way to advance a field is an advancement in the technical capabilities that allows new perspectives to be reached.
使用 NMR 测量弛豫时间来研究蛋白质动力学的方法基于 20 世纪中期的一系列研究，这些研究概述了相关理论和方法。然而，由于蛋白质 NMR 的复杂性，这些简单的实验并不适用于蛋白质。20 世纪 80 年代，用于蛋白质同位素标记的技术的出现意味着现在可以在多维 NMR 实验中应用脉冲序列，从而获得关于局部弛豫时间的每个残基的信息。最早的进展之一发表于 1989 年。Lewis Kay、Dennis Torchia 和 Ad Bax 的论文“通过 N 反向检测异核 NMR 光谱研究蛋白质的骨架动力学：在葡萄球菌核酸酶中的应用”概述了一组脉冲序列，即使在今天也只有一些细微的修改。即使在今天，这篇论文和其他少数几个实验室的其他论文仍然是确定蛋白质骨架动力学的实验基础。在过去的 30 年里，从这些测量中获得的生物学见解只增不减。有时，推进一个领域的最好的、也许是唯一的方法是技术能力的进步，这可以让人们获得新的视角。
