National Resource for Advanced NMR Technology

国家先进核磁共振技术资源

• 批准号: 10568406
• 负责人: William W Brey
• 金额: $ 134.45万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10568406
• 关键词: Address; Amino Acids; Applied Research; Area; Automobile Driving; Bacterial Drug Resistance; Basic Science; Biochemical; Biological; Biology; Biomedical Research; Biomedical Technology; Biopolymers; Cell Wall; Chemicals; Chemistry; Communities; Complex; Complex Mixtures; Cryoelectron Microscopy; Dedications; Disease; Drug Targeting; Education; Educational Activities; Educational workshop; Electronics; Electrons; Environment; Funding; Gene Expression Regulation; Generations; Goals; High temperature of physical object; Hybrids; Hydrogen; Information Technology; Infrastructure; International; Kinetics; Laboratories; Licensing; Macromolecular Complexes; Mass Spectrum Analysis; Measures; Membrane Proteins; Mentors; Metabolic; Metals; Microbial Biofilms; Mycoses; NMR Spectroscopy; Nuclear; Nuclear Magnetic Resonance; Positioning Attribute; Process; Proteins; Protons; Publications; RF coil; Regulation; Research; Research Personnel; Resolution; Resources; Roentgen Rays; Sampling; Science; Scientist; Series; Services; Signal Transduction; Structural Biochemistry; Structure; Structure-Activity Relationship; Technology; Temperature; Training; Training Activity; Training and Education; United States National Institutes of Health; Work; X-Ray Crystallography; analytical tool; biomedical scientist; cold temperature; community engagement; design and construction; drug development; drug resistance development; enzyme mechanism; frontier; improved; insight; instrument; instrumentation; kinetic model; lectures; macromolecule; magnetic field; meetings; metabolomics; new technology; news; non-alcoholic fatty liver disease; novel; open data; outreach; programs; scientific organization; solid state nuclear magnetic resonance; structural biology; technology development; tool; web site

Nuclear magnetic resonance (NMR) spectroscopy is a unique set of experimental tools for understanding the intricacies of biology, from macromolecular complexes to complex mixtures, from atomic resolution structure to dynamics on timescales of picoseconds to seconds, from chemistry to functional mechanisms and kinetic processes. No other technology has such breadth and potential for basic and applied research and for interfacing with other technologies, such as X-ray crystallography, small angle X-ray scattering, Cryo-EM, mass spectrometry, and many other spectroscopic and analytical tools. Structural characterization serves as the framework for using NMR to understand biological activities, protein-protein and protein interface interactions, functional mechanisms, and kinetic models. Dynamics can be exceptionally well characterized by NMR, which can lead to detailed understanding about how proteins and other macromolecules function, how complexes are formed, and how certain kinetic processes and rates are achieved. The solution NMR spectroscopy of complex mixtures is particularly useful in combination with mass spectrometry for metabolomics and other complex mixtures, whereas solid-state NMR (ssNMR) is uniquely capable of measuring chemical shift and quadrupolar tensors to provide insights into chemical biology. Here, we focus on the frontiers of NMR technology made possible by recent breakthroughs in materials research and instrumentation, and their implementation for a broad user community pursuing fundamental questions at atomic resolution at the forefront of biomedical research. Three Technology Development Projects (TDP) advance the sensitivity of NMR, each featuring novel technologies. TDP1 features the use of high temperature superconductors (HTS) for RF coils, leading to high sensitivity for solution NMR spectroscopy. TDP2 takes advantage of our 600 MHz MAS-DNP NMR instrument, which will provide enhanced sensitivity through the transfer of magnetization from electrons to protons. New and much more robust DNP probes with expanded temperature ranges will be developed. TDP3 uses the 36 T Series Connected Hybrid (36T-SCH) and all-HTS 32 T superconducting (32T-SCM) magnets for ssNMR and solution NMR spectroscopy – the 36T-SCH is the highest-field NMR spectrometer in the world, and the 32T-SCM will be the highest-field spectrometer with low-temperature (4-30 K) capabilities for NMR explorations of biosolids. These platforms will lead to dramatic enhancements in sensitivity and spectacular reductions in signal averaging times. The science will be driven by a select team of ten scientists with Driving Biomedical Projects (DBP), and over 30 Collaborative and Service Projects (CSP) and Technology Partnership Projects (TPP) that span a very broad range of biomedical and biochemical research areas. A major team effort will be placed on training a new generation of NMR users through annual workshops, as well as dissemination through publications and presentations at meetings, a wide variety of scientific organizations, news media, a dedicated website for this Resource, training and educational activities, and posting of training lectures and videos of demonstrations.

核磁共振（NMR）光谱是一组独特的实验工具，用于理解 来自原子分辨率结构的生物学的复杂性，从大分子复合物到复杂的混合物 从化学到功能机制和动力学 过程。没有其他技术具有基础研究和应用研究的宽广和潜力，并进行接口 与其他技术，例如X射线晶体学，小角度X射线散射，冷冻EM，质量 光谱法以及许多其他光谱和分析工具。结构表征是 使用NMR了解生物活性，蛋白质 - 蛋白质和蛋白质界面相互作用的框架， 功能机理和动力学模型。动力学可以是NMR的特征，它可以很好地表征 可能会导致人们对蛋白质和其他大分子如何发挥作用，复合物的详细理解 形成，以及如何实现某些动力学过程和速率。复合物的溶液NMR光谱 混合物在与代谢组和其他复合物的质谱结合使用方面特别有用 混合物，而固态NMR（SSNMR）具有独特的能力测量化学位移和四极了 张量提供有关化学生物学的见解。在这里，我们专注于NMR技术的前沿 最近在材料研究和仪器方面的突破以及它们实施广泛的实施可能是可能的 用户社区在生物医学研究的最前沿，在原子分辨率上提出基本问题。 三个技术开发项目（TDP）提高了NMR的敏感性，每个NMR都具有小说 技术。 TDP1具有用于RF线圈的高温超导体（HTS）的使用，导致高温 溶液NMR光谱的敏感性。 TDP2利用我们的600 MHz MAS-DNP NMR仪器， 这将通过将磁化从电子转移到质子来提供增强的灵敏度。新和 随着温度范围的扩大，更强大的DNP问题将被开发出来。 TDP3使用36 T系列 连接的杂种（36T-SCH）和全HTS 32 T超导（32T-SCM）磁铁，用于SSNMR和溶液 NMR光谱学 - 36T-SCH是世界上最高的NMR光谱仪，32T-SCM将是 具有低温（4-30 K）功能的最高场光谱仪可用于NMR的生物固体探索。 这些平台将导致信号平均的灵敏度和壮观降低的显着增强 时代。该科学将由一支由十个科学家组成的精选团队驱动生物医学项目（DBP），并且 超过30多个合作和服务项目（CSP）和技术合作伙伴项目（TPP），这些项目非常跨度 广泛的生物医学和生化研究领域。将在培训新的方面进行重大团队的努力 通过年度研讨会以及通过出版物传播和传播NMR用户的生成 会议上的演讲，各种科学组织，新闻媒体，一个专门的网站 资源，培训和教育活动，以及培训讲座和演示视频的发布。