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：利用动态核极化的生物医学研究 项目摘要/摘要 动态核极化（DNP）的发展，以提高NMR的灵敏度1-2 大小对NMR领域产生了深远的影响。早期结果证明了DNP的实用性 结合魔术角旋转（MAS）固态NMR（SSNMR）用于生物分子研究提供动力 为了进一步开发DNP技术以支持生物医学研究应用。此TR＆D地址 NMR社区面临的挑战使DNP成为真正的正交的，可以实现生物分子的技术 SSNMR通过三个特定目的：1）开发具有灵活电子体系结构的DNP MAS SSNMR探针， 快速MAS和扩展VT范围； 2）开发一个Biradical工具箱，用于针对特定的DNP增强 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，以通过硬件最大化DNP的承诺 开发，所需化学试剂的合成，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。所有这些进步 必须追求领域，以获得领先的生物医学研究所需的敏感性和解决方案 应用和将DNP MAS SSNMR转换为结构性更广泛访问的技术 整个生物学社区。通过与六个驾驶生物医学研究项目合作，我们将 在此TR＆D中迅速开发和部署技术，以解决在此领域的生物医学研究问题 膜蛋白结构测定，细菌生物膜中的淀粉样生物发生以及神经培养 疾病，病毒中的蛋白质组装和酶催化。