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）光谱是一套独特的实验工具， 生物学的复杂性，从大分子复合物到复杂的混合物，从原子分辨率结构 到皮秒到秒的时间尺度上的动力学，从化学到功能机制和动力学 流程.没有其他技术具有这样的广度和潜力，用于基础和应用研究以及接口 与其他技术，如X射线晶体学，小角X射线散射，冷冻EM，质量 光谱法和许多其他光谱和分析工具。结构表征作为 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， 功能机制和动力学模型。NMR可以非常好地表征动力学， 可以详细了解蛋白质和其他大分子的功能，复合物是如何 形成，以及如何实现某些动力学过程和速率。配合物的溶液核磁共振谱 混合物特别可与质谱法结合用于代谢组学和其它复杂的生物学分析。 混合物，而固态NMR（ssNMR）是唯一能够测量化学位移和四极 张量来提供对化学生物学的见解。在这里，我们重点介绍核磁共振技术的前沿进展 最近在材料研究和仪器方面的突破，以及它们在广泛领域的应用， 在生物医学研究的前沿追求原子分辨率的基本问题的用户社区。 三个技术开发项目（TDP）提高了NMR的灵敏度，每个项目都具有新颖的 技术. TDP 1的特点是使用高温超导体（HTS）的RF线圈，导致高 溶液NMR光谱的灵敏度。TDP 2利用我们的600 MHz MAS-DNP NMR仪器， 这将通过磁化从电子到质子的转移提供增强的灵敏度。新的和 将开发具有扩展的温度范围的更坚固的DNP探针。TDP 3采用36 T系列 用于ssNMR和溶液的连接混合（36 T-SCH）和全HTS 32 T超导（32 T-SCM）磁体 NMR光谱仪-36 T-SCH是世界上最高场NMR光谱仪，32 T-SCM将成为 具有低温（4-30 K）能力的最高场谱仪，用于生物固体的NMR探测。 这些平台将导致灵敏度的显著增强和信号平均的显著降低 次科学将由一个由十名科学家组成的精选团队与驾驶生物医学项目（DBP）一起推动， 超过30个合作和服务项目（CSP）和技术伙伴关系项目（TPP）， 广泛的生物医学和生物化学研究领域。一个主要的团队努力将放在培训一个新的 通过年度讲习班培养核磁共振用户，并通过出版物进行传播， 会议上的演讲，各种各样的科学组织，新闻媒体，一个专门的网站， 资源、培训和教育活动，以及张贴培训讲座和演示视频。