DEVELOPMENTS IN STUDIES OF BIOMACROMOLECULES

该项目的主要目的是开发新技术， 在高分辨率、二维、高分辨率 NMR光谱学在结构和性质研究中的应用 生物大分子如蛋白质和 核酸 最近介绍的实验涉及相干转移通过 核各向同性混合和磁化转移 研究了旋转坐标系下的Overhauser效应 具有促进共振分配的巨大潜力， 获得用于结构确定的距离约束， 分别 然而，在实践中， 在各向同性混合实验中， 理论上的特征，也没有精确的行为， 双标架NOE中的相干传递途径 实验;在后一个实验中， 其外观与有效横向NOE峰相同 而这些都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 对这些实验进行深入的理论分析， 优化它们以用于生物分子的研究。 该项目的另一个目标将是执行一个理论 多量子交换效应研究 谱 核磁共振光谱是一种非常重要的工具， 研究交换现象，并已被雇用 在单量子实验中以各种方式广泛应用。 没有描述多量子交换效应 然而，还没有提供光谱学。 受的这种影响而 多个量子光谱可以提供关于 单量子交换系统无法实现的交换系统 实验 然而，二维NMR光谱具有 提供大量信息的潜力， 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率的测量 例如碳-13可以用于确定运动相关性 分子内局部碎片的时间。 缺乏敏感性 是测量这种弛豫速率的主要问题; 目前的建议努力将致力于开发新的 获得稀有核弛豫率的方法 提高灵敏度。 此外，修饰的序列用于 记录异质结相关谱将在 试图改善对不良信号的抑制。 在过去的五年里，许多新的2D NMR技术已经 被提议用于研究蛋白质和核酸。 的 这些技术的有效性主要取决于 2D光谱中可用的信息量，这反过来又 取决于这种光谱的质量。 中的建议是 目前的项目，以审查提高质量的可能性 的光谱，获得与目前的方法， 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.