Shen Yang, Bax Ad
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Struct Dyn. 2023 Jul 11;10(4):040901. doi: 10.1063/4.0000192. eCollection 2023 Jul.
The important role of structural dynamics in protein function is widely recognized. Thermal or B-factors and their anisotropy, seen in x-ray analysis of protein structures, report on the presence of atomic coordinate heterogeneity that can be attributed to motion. However, their quantitative evaluation in terms of protein dynamics by x-ray ensemble refinement remains challenging. NMR spectroscopy provides quantitative information on the amplitudes and time scales of motional processes. Unfortunately, with a few exceptions, the NMR data do not provide direct insights into the atomic details of dynamic trajectories. Residual dipolar couplings, measured by solution NMR, are very precise parameters reporting on the time-averaged bond-vector orientations and may offer the opportunity to derive correctly weighted dynamic ensembles of structures for cases where multiple high-resolution x-ray structures are available. Applications to the SARS-CoV-2 main protease, M, and ubiquitin highlight this complementarity of NMR and crystallography for quantitative assessment of internal motions.
结构动力学在蛋白质功能中的重要作用已得到广泛认可。在蛋白质结构的X射线分析中观察到的热因子或B因子及其各向异性，反映了可归因于运动的原子坐标异质性的存在。然而，通过X射线系综精修对其在蛋白质动力学方面进行定量评估仍然具有挑战性。核磁共振光谱提供了关于运动过程的幅度和时间尺度的定量信息。不幸的是，除了少数例外情况，核磁共振数据并不能直接洞察动态轨迹的原子细节。通过溶液核磁共振测量的剩余偶极耦合是非常精确的参数，可报告时间平均键矢量方向，并可能为有多个高分辨率X射线结构的情况提供推导正确加权的结构动态系综的机会。对严重急性呼吸综合征冠状病毒2主蛋白酶、M蛋白和泛素的应用突出了核磁共振和晶体学在定量评估内部运动方面的这种互补性。
