TR&D2-DNP

Tr&d2：利用动态核极化的生物医学研究 项目摘要/摘要 将核磁共振灵敏度提高1-2个数量级的动态核极化技术的发展 震级正深刻地影响着核磁共振领域。早期结果证明了DNP在以下情况下的实用性 与魔角旋转(MAS)相结合的固体核磁共振(ss核磁共振)为生物分子研究提供了动力 用于进一步开发DNP技术，以支持生物医学研究应用。这是一项研究与开发工作 核磁共振社区在使DNP成为真正正交的、使能用于生物分子的技术方面面临挑战 通过三个特定的目的：1)开发具有灵活电子结构的DNP MAS单核磁共振探针， 快速MAS和扩展的VT范围；2)开发针对特定DNP增强的双基工具箱 蛋白质类；以及3)优化DNP MAS单核磁共振生物分子结构测定方法。这个 这些目标的目标是提供一种整体方法，通过硬件最大化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 发展DNP时代的生物分子单核磁共振实验框架。所有这些方面的进展 必须追求的领域，以获得前沿生物医学研究所需的敏感性和分辨率 应用程序，并将DNP MAS单核磁共振过渡到一种更广泛地适用于结构 生物界作为一个整体。通过与六个推动生物医学研究项目的合作，我们将 在这一研发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 细菌生物膜和神经退行性变中的膜蛋白结构测定、淀粉样蛋白的生物发生 疾病、病毒中的蛋白质组装和酶催化。

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.