Random Phase Detection for Accelerating Biomolecular NMR Experiments

描述（由申请人提供）：用于加速生物分子NMR实验的随机相位检测高分辨率NMR光谱学是在溶液条件下研究生物分子系统的有力工具，与细胞或血液中遇到的生物分子系统相当。它是唯一能够以原子分辨率确定溶液中三维结构的方法。它也可以应用于高度动态或内在无序的生物分子，不能通过X射线晶体学研究。它是唯一能够确定的程度和速度的结构波动的解决方案，并有越来越多的认识，了解蛋白质动力学是必不可少的了解他们的生物功能。它也是一种探测生物分子相互作用的强有力的方法，在药物发现中有重要的应用。虽然显着的技术进步，使核磁共振的应用越来越复杂的生物分子系统，高场磁体提供的全部潜在的分辨率通常不会实现沿着所有维度的多维实验，由于测量时间的实际限制。通过采用不需要以均匀间隔对数据进行采样的谱分析的非傅立叶方法，使用实际量的测量时间在多维NMR实验中实现高得多的分辨率变得可能。限制缩短NMR实验的能力的一个因素是需要确定信号分量的频率的符号。确定符号的常规方法强加了两倍的采样负担。我们最近发现，检测信号的相位随机变化（随机相位检测）的方法使得能够确定频率的符号而不施加两倍的采样负担。该建议的目的是探索在减少实验时间和/或提高生物分子的多维NMR实验的分辨率，通过结合随机相位检测在时间上的非均匀采样，可以实现的收益。对生物分子进行多维NMR实验所需时间的进一步减少将使高维实验变得实用，并将适用性扩展到快速稳定的系统。重要的是，它们将使高场磁体所提供的全部潜在分辨率能够在多维实验的间接维度中实现，从而扩展适合NMR研究的系统的大小和复杂性。相反，减少的采样要求可用于增加多维NMR的灵敏度，有助于促进对微溶或丰度差的生物分子的研究。

DESCRIPTION (provided by applicant): Random Phase Detection for Acceleration of Biomolecular NMR Experiments High resolution NMR spectroscopy is a powerful tool for investigating biomolecular systems under solution conditions comparable to those encountered in the cell or blood. It is the only method capable of determining 3-dimensional structure in solution with atomic resolution. It also can be applied to highly dynamic or intrinsically disordered biomolecules that cannot be studied by x-ray crystallography. It is uniquely capable of determining both the extent and rate of structural fluctuations in solution, and there is a growing appreciation that understanding protein dynamics is essential for understanding their biological functions. It also a powerful method for probing biomolecular interactions, and has important applications in drug discovery. Although remarkable advances in technology have enabled the application of NMR to increasingly complex biomolecular systems, the full potential resolution afforded by high field magnets is generally not achieved along all the dimensions of multidimensional experiments due to practical limits on measuring time. By employing non- Fourier methods of spectrum analysis that do not require data to be sampled at uniform intervals, it is becoming possible to achieve much higher resolution in multidimensional NMR experiments using practical amounts of measuring time. A factor limiting the ability to shorten NMR experiments is the need to determine the sign of the frequency of signal components. Conventional approaches to determining the sign impose a factor of two sampling burden. We recently discovered that an approach in which the phase of the detected signal is randomly varied (random phase detection) enables determination of the sign of the frequency without imposing a factor of two sampling burden. The aim of this proposal is to explore the gains that can be achieved in reducing experiment time and/or improving resolution in multidimensional NMR experiments on biomolecules by combining nonuniform sampling in time with random phase detection. Further reductions in the time required to conduct multidimensional NMR experiments on biomolecules will render highly- dimensional experiments practical and extend applicability to systems that are fleetingly stable. Importantly, they will enable the full potentil resolution afforded by high-field magnets to be realized in the indirect dimensions of multidimensional experiments, extending the size and complexity of systems amenable to NMR investigation. Conversely, the reduced sampling requirements can be used to increase the sensitivity of multidimensional NMR, helping to facilitate the investigation of sparingly soluble o poorly abundant biomolecules.