TR&D2-DNP

TR&D2：利用动态核极化的生物医学研究 项目概要/摘要 动态核极化（DNP）技术的发展使核磁共振的灵敏度提高了1-2个数量级。 巨大的能量正在深刻地影响着核磁共振领域。早期结果证明了DNP的效用， 结合魔角旋转（MAS）固态核磁共振（ssNMR）为生物分子研究提供了动力 进一步开发DNP技术，以支持生物医学研究应用。本TR&D解决了 NMR社区在使DNP成为真正正交的生物分子识别技术方面面临的挑战 ssNMR通过三个具体目标：1）开发具有灵活电子结构的DNP MAS ssNMR探针， 快速MAS和扩展VT范围; 2）开发双自由基工具箱，用于靶向DNP增强特定 蛋白质类;和3）优化用于生物分子结构测定的DNP MAS ssNMR方法。的 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实现DNP的承诺 开发、合成所需的化学试剂、优化样品制备策略，以及 在DNP时代发展生物分子ssNMR的实验框架。所有这些方面的进展 为了获得前沿生物医学研究所需的灵敏度和分辨率， 应用程序和过渡DNP MAS ssNMR的技术，更广泛地访问的结构 生物学作为一个整体。通过与六个驱动生物医学研究项目的合作，我们将 在本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，细菌生物膜中的淀粉样蛋白生物发生和神经变性 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.