DEVELOPMENTS IN 2D NMR STUDIES OF BIOMACROMOLECULES

这个项目的主要目标是开发新技术和 改进现有方法在高分辨率、二维 核磁共振波谱在结构和结构研究中的应用 蛋白质和蛋白质等生物大分子的动力学 核酸。 最近引入的实验涉及相干传输通过 原子核的各向同性混合和磁化传递 旋转框架中的Overhauser效应(NOE)已显示 具有促进共鸣任务的巨大潜力，并 获取用于结构确定的距离约束， 分别进行了分析。然而，在实践中，连贯转移 各向同性混合实验中的过程不是很好 从理论上讲，也没有准确的行为 旋转框架NOE中的相干转移路径 实验；在后一个实验中，可以获得人工制品 它们在外观上与有效的横向NOE峰相同 它们是通过相干转移的存在而产生的 流程。该项目的一个目标是开展一项 对这些实验进行彻底的理论分析，并 优化它们以用于生物分子的研究。 这个项目的另一个目标将是执行一个理论上的 多量子交换效应的研究 光谱学。核磁共振波谱是一种非常重要的工具 研究交换现象，并已被用于 在单量子实验中以各种方式广泛应用。 没有对多量子交换效应的描述 然而，光谱学还没有提供。这样的影响在 多个量子光谱可以提供关于 单个量子系统无法提供的交换系统 实验。 异核、二维核磁共振波谱具有 在研究中提供丰富信息的潜力 生物分子的结构和动力学。特别是， 选定原子核的核磁共振弛豫速率的测量 例如碳-13可以用来确定运动相关性 分子中局部片段的时间。缺乏敏感度 是衡量这种松弛速率的一个主要问题；在 目前的提案工作将针对开发新的 稀有核弛豫率的计算方法 提高了灵敏度。此外，修改的序列用于 记录异核关联光谱将在#年进行研究 一种改善对不良信号抑制的尝试。 在过去五年左右的时间里，许多新的2D核磁共振技术已经 已被提议用于研究蛋白质和核酸。这个 这些技术的有效性在很大程度上取决于 2D光谱中可用的信息量，这反过来又 取决于这些光谱的质量。它是在 目前的项目是检查提高质量的可能性 通过以下方式使用当前方法获得的光谱 修改脉冲序列、采集参数和数据 处理程序。

The major aim of this project is to develop new techniques and to improve existing methods in high-resolution, Two-dimensional NMR spectroscopy for applications in studies of the structure and dynamics of biological macromolecules such as protein and nucleic acids. Recently introduced experiments involving coherence transfer via isotropic mixing and magnetization transfer via nuclear Overhauser effects (NOE) in the rotating frame have been shown to have great potential for facilitating resonance assignments and obtaining distance constraints for structural determinations, respectively. However, in practical terms the coherence transfer process in the isotropic mixing experiment has not been well characterized theoretically, nor has the precise behaviour of coherence transfer pathways in the rotating-frame NOE experiment; in the latter experiment artifacts can be obtained which are identical in appearance to valid transverse NOE peaks and which arise through the presence of coherence transfer processes. One goal of this project will be to carry out a thorough, theoretical analysis of these experiments and to optimize them for use in studies of biomolecules. Another goal of this project will be to perform a theoretical investigation of exchange effects in multiple quantum spectroscopy. NMR spectroscopy is a very important tool for examining exchange phenomena, and has been employed extensively in a variety of ways in single quantum experiments. No description of exchange effects in multiple quantum spectroscopy has yet been provided, however. Such effects in multiple quantum spectra can provide unique information about exchanging systems which is not available from single quantum experiments. Heteronuclear, two-dimensional NMR spectroscopy has the potential of supplying a wealth of information in studies of the structure and dynamics of biomolecules. In particular, measurements of the NMR relaxation rates of selected nuclei such as carbon-13 can be used to determine motional correlation times for local fragments within a molecule. Lack of sensitivity is a major problem in measuring such relaxation rates; in the present proposal efforts will be directed towards developing new methods for obtaining relaxation rates of rare nuclei with improved sensitivity. In addition, modified sequences for recording heteronuclear correlation spectra will be investigated in an attempt to improve the suppression of undesirable signals. Over the last five years or so many new 2D NMR techniques have been proposed for use in studying proteins sand nucleic acids. The usefulness of these techniques is largely determined by the amount of information available in the 2D spectra, which in turn is dependent on the quality of such spectra. It is proposed in the present project to examine the possibility of improving the quality of spectra which are obtained with current methodologies by modifying the pulse sequences, acquisition parameters, and data processing procedures.