Extreme Nonuniform Sampling for Protein NMR Dynamics Studies in Minimal Time
Extreme Nonuniform Sampling for Protein NMR Dynamics Studies in Minimal Time
复制标题
在最短时间内进行蛋白质 NMR 动力学研究的极端非均匀采样
DOI：
10.1021/jacs.9b08032
复制
发表时间：
2019
影响因子：
15
通讯作者：
Brüschweiler, Rafael
中科院分区：
文献类型：
--
作者：
Jameson, Gregory;Hansen, Alexandar L.;Li, Dawei;Bruschweiler-Li, Lei;Brüschweiler, Rafael
NMR光谱是使用自旋弛豫或化学交换饱和转移（CEST）实验的溶液中蛋白质的定量动力学的非常丰富的来源。然而，15 N-CEST测量需要长时间的多维，所谓的伪3D HSQC实验，其中伪维度是弱15 N饱和场的射频偏移Δω。非均匀采样（NUS）方法有可能显着加快这些测量，但它们也带来了引入严重的文物和非均匀采样时间表的系统优化的风险仍然难以捉摸。这里展示了如何通过使用参考2D HSQC实验的拟合交叉峰作为足迹来解决这一挑战，随后通过线性最小二乘拟合将其用于重建伪3D数据集的交叉峰幅度作为Δω的函数。它示出了蛋白质Im 7的方法如何可以产生高度准确的CEST配置文件的基础上，绝对最低限度采样（AMS）的数据集，允许一个因素20-30的加速。基于Cramer-Rao下界度量的频谱特定优化非均匀采样（SONUS）方案对于实现这样的性能至关重要，也揭示了最优采样方案的更一般性质。这是首次系统地探索和优化NUS时间表，以大幅加速定量多维NMR测量，最大限度地减少不必要的错误。
NMR spectroscopy is an extraordinarily rich source of quantitative dynamics of proteins in solution using spin relaxation or chemical exchange saturation transfer (CEST) experiments. However,15N-CEST measurements require prolonged multidimensional, so-called pseudo-3D HSQC experiments where the pseudo dimension is a radio frequency offset Δω of a weak15N saturation field. Nonuniform sampling (NUS) approaches have the potential to significantly speed up these measurements, but they also carry the risk of introducing serious artifacts and the systematic optimization of nonuniform sampling schedules has remained elusive. It is demonstrated here how this challenge can be addressed by using fitted cross-peaks of a reference 2D HSQC experiment as footprints, which are subsequently used to reconstruct cross-peak amplitudes of a pseudo-3D data set as a function of Δω by a linear least-squares fit. It is shown for protein Im7 how the approach can yield highly accurate CEST profiles based on an absolutely minimally sampled (AMS) data set allowing a speed-up of a factor 20–30. Spectrum-specific optimized nonuniform sampling (SONUS) schemes based on the Cramer–Rao lower bound metric were critical to achieve such a performance, revealing also more general properties of optimal sampling schedules. This is the first systematic exploration and optimization of NUS schedules for the dramatic speed-up of quantitative multidimensional NMR measurements that minimize unwanted errors.