TR&D2-DNP

TR

• 批准号: 10217178
• 负责人: Joanna R Long
• 金额: $ 12.67万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10217178
• 关键词: Address; Age; Amyloid; Architecture; Area; Automobile Driving; Behavior; Biogenesis; Biological; Biomedical Research; Biomolecular Nuclear Magnetic Resonance; Catalysis; Cell Nucleus; Chemicals; Communities; Complex; Congo Red; Dependence; Development; Disease; Effectiveness; Electrons; Enzymes; Equilibrium; Face; Freezing; Frequencies; Goals; Heating; Integral Membrane Protein; Investments; Isotopes; Link; Lipids; Magic; Membrane Proteins; Methods; Microbial Biofilms; Molecular; Molecular Target; Multidimensional NMR Techniques; Noise; Nuclear; Optics; Pathway interactions; Preparation; Property; Proteins; Reagent; Research Project Grants; Resolution; Resources; Sampling; Senile Plaques; Signal Transduction; Site; Source; Spin Labels; Structure; Sulfhydryl Compounds; System; Techniques; Technology; Temperature; Viral; Virus; Width; base; cold temperature; cryogenics; experimental study; flexibility; holistic approach; improved; interest; magnetic field; microwave electromagnetic radiation; particle; protein structure; solid state nuclear magnetic resonance; structural biology; technology development

TR&D2: Biomedical Research Utilizing Dynamic Nuclear Polarization Project Summary/Abstract The development of dynamic nuclear polarization (DNP) to increase the sensitivity of NMR by 1-2 orders of magnitude is profoundly impacting the field of NMR. Early results demonstrating the utility of DNP when combined with magic angle spinning (MAS) solid state NMR (ssNMR) for biomolecular studies provide impetus for further developing DNP technology to support biomedical research applications. This TR&D addresses challenges the NMR community faces in making DNP a truly orthogonal, enabling technology for biomolecular ssNMR through three specific aims: 1) develop DNP MAS ssNMR probes with flexible electronic architecture, fast MAS, and extended VT Range; 2) develop a biradical toolbox for targeted DNP enhancement of specific protein classes; and 3) optimize DNP MAS ssNMR approaches for biomolecular structure determination. The goal of these aims is to provide a holistic approach to maximizing the promise of DNP through hardware development, synthesis of needed chemical reagents, optimization of sample preparation strategies, and developing the experimental framework for biomolecular ssNMR in the age of DNP. Advances in all these areas must be pursued to gain the needed sensitivity and resolution for leading edge biomedical research applications and to transition DNP MAS ssNMR to a technique that is more widely accessible to the structural biology community as a whole. Through partnering with six Driving Biomedical Research projects, we will rapidly develop and deploy technology in this TR&D to address biomedical research problems in the areas of membrane protein structure determination, amyloid biogenesis in bacterial biofilms and in neurodenerative diseases, protein assembly in viruses, and enzyme catalysis.

TR&D2：利用动态核极化进行生物医学研究 项目概要/摘要 动态核极化（DNP）的发展使NMR的灵敏度提高了1-2个数量级 震级正在深刻地影响核磁共振领域。早期结果证明了 DNP 的实用性 与魔角旋转 (MAS) 固态核磁共振 (ssNMR) 相结合，为生物分子研究提供动力 进一步开发 DNP 技术以支持生物医学研究应用。此 TR&D 解决了 NMR 界在使 DNP 成为真正正交的生物分子支持技术方面面临的挑战 ssNMR 通过三个具体目标：1）开发具有灵活电子架构的 DNP MAS ssNMR 探针， 快速 MAS 和扩展 VT 范围； 2) 开发一个双自由基工具箱，用于有针对性地增强特定的 DNP 蛋白质类别； 3) 优化用于生物分子结构测定的 DNP MAS ssNMR 方法。这 这些目标的目标是提供一种整体方法，通过硬件最大限度地发挥 DNP 的承诺 所需化学试剂的开发、合成，样品制备策略的优化，以及 开发 DNP 时代生物分子 ssNMR 的实验框架。所有这些方面的进步 必须追求的领域以获得前沿生物医学研究所需的灵敏度和分辨率 应用，并将 DNP MAS ssNMR 转变为结构更广泛可用的技术 整个生物学界。通过与六个驱动生物医学研究项目合作，我们将 在此 TR&D 中快速开发和部署技术，以解决以下领域的生物医学研究问题 膜蛋白结构测定、细菌生物膜和神经变性中的淀粉样蛋白生物发生 疾病、病毒中的蛋白质组装和酶催化。