DEVELOPMENT OF 2D AND 3D NMR FOR STUDIES OF BIOMOLECULES

用于生物分子研究的 2D 和 3D NMR 的发展

• 批准号: 2180166
• 负责人: MARK A RANCE
• 金额: $ 15.79万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2180166
• 关键词: biomedical equipment development; clinical biomedical equipment; drug receptors; enzyme substrate; macromolecule; molecular dynamics; nuclear magnetic resonance spectroscopy; nucleic acid structure; protein structure; quantum chemistry

The major goal of this project is the development of new, high resolution nuclear magnetic resonance (NMR) methodologies for use in studies of the structure and dynamics of biomolecules such as proteins and nucleic acids. NMR spectroscopy has become an extremely powerful tool for the study of biomolecules in solution, due to its ability to provide detailed information at an atomic level The extent to which NMR spectroscopy can be exploited for three-dimensional structure determinations of biomolecules, the investigation of intermolecular interactions in systems such as drug/receptor, enzyme/substrate and antibody/antigen complexes, and the characterization of the dynamics of molecular fragments, will depend on the ability to manipulate the system to yield EM desired information. The enormous contribution that biological NMR has made during the last decade in the investigation of biomolecules and biophysical processes is due largely to the continuing development of new or improved techniques for extracting useful data from the systems of interest. A prerequisite step in any NMR study is the assignment of resonances to individual nuclei in the molecule of interest. One of the most efficient experiments currently in use for resonance assignment is based on the principle of isotropic mixing. Despite the popularity of such experiments, they have not been well characterized theoretically. One aim of the proposed research is a detailed analysis and development of various aspects of isotropic mixing experiments, in particular, the development of novel schemes employing multiple frequency irradiation to improve the efficiency. Also, new experiments employing isotropic mixing for heteronuclear coherence transfer will be explored. In the development of new NMR techniques and the analysis of their characteristics, it is common to make simplifying assumptions. However, in some of the most recent experiments, especially those employing long periods of radio-frequency irradiation, it is necessary to conduct a more rigorous analysis which includes the effects of NMR relaxation phenomena. It is vital to consider relaxation processes in the development of new experiments designed to separate the effects of relaxation and coherence transfer. One of the major goals in this proposal is to derive a convenient formalism for including relaxation effects into NMR simulations, and to use this for the development of improved isotropic mixing and related techniques. While NMR is the method of choice for obtaining detailed information in physical studies of biomolecules in solution, it unfortunately is a comparatively insensitive technique. It is proposed to investigate promising schemes for improving the sensitivity of various, important techniques such as isotropic mixing, heteronuclear correlation methods and relaxation time measurements. Theoretically, the new experiments to be developed can reduce the required measuring time in half. Dynamical processes in biomolecular systems often play a key role in biological function, and thus it is very important to have suitable methods for characterizing such phenomena. NMR spectroscopy is a very powerful tool for obtaining detailed information on the dynamics of molecular fragments. One important aim of this proposal is to characterize theoretically and demonstrate the usefulness of multiple quantum techniques for studying chemical reorganization processes. Another major goal is to develop techniques which will facilitate the measurement of heteronuclear relaxation rates. Such data would be invaluable for use in functional and structural studies of biomolecules such as proteins and nucleic acids.

该项目的主要目标是开发新的高分辨率 用于研究的核磁共振（NMR）方法 生物分子的结构和动力学，例如蛋白质和核酸。 NMR光谱已成为研究的极其强大的工具 溶液中的生物分子，由于其能够提供详细的能力 在原子能级别的信息可以是NMR光谱的程度 利用用于生物分子的三维结构确定， 研究系统中分子间相互作用的研究 药物/受体，酶/底物和抗体/抗原复合物，以及 分子碎片动力学的表征将取决于 能够操纵系统以产生所需信息的能力。 这 生物NMR在过去十年中所做的巨大贡献 在研究生物分子和生物物理过程中 在很大程度上是为了持续开发新的或改进的技术 从感兴趣的系统中提取有用的数据。 任何NMR研究中的先决条件是共振的分配 在感兴趣的分子中单个核。 最大的 当前正在使用共振分配的有效实验是基于的 根据各向同性混合的原理。 尽管很受欢迎 实验，它们在理论上没有得到很好的表征。 一个目的 拟议的研究是各种详细的分析和开发 各向同性混合实验的各个方面，特别是 采用多频率照射的新型方案来改善 效率。 此外，采用各向同性混合的新实验 将探索异核一致性转移。 在开发新的NMR技术及其分析中 特征，通常做出简化的假设。 然而， 在最近的一些实验中，尤其是那些使用长期的实验 射频辐射的时期，有必要进行更多 严格的分析，包括NMR松弛现象的影响。 考虑新的发展过程至关重要 旨在分开放松和连贯性的效果的实验 转移。 该提案的主要目标之一是得出 方便的形式主义将放松效应包括在NMR模拟中， 并将其用于开发改进的各向同性混合和 相关技术。 虽然NMR是获得详细信息的首选方法 在溶液中生物分子的物理研究中，不幸的是 相对不敏感的技术。 提议调查 有希望的方案，以提高各种重要的，重要的 诸如各向同性混合，异核相关方法等技术和 放松时间测量。 从理论上讲，新实验是 开发可以将所需的测量时间减少一半。 生物分子系统中的动态过程通常在 生物学功能，因此拥有合适的方法非常重要 用于表征这种现象。 NMR光谱学是非常强大的 获取有关分子动力学的详细信息的工具 碎片。 该提议的一个重要目的是表征 从理论上讲并证明多种量子技术的实用性 用于研究化学重组过程。 另一个主要目标是 开发技术将有助于测量异核 放松率。 此类数据对于功能和 生物分子（例如蛋白质和核酸）的结构研究。