RM1 Center on Macromolecular Dynamics by NMR Spectroscopy at the New York Structural Biology Center (CoMD/NMR)

纽约结构生物学中心 (CoMD/NMR) 的 RM1 核磁共振波谱大分子动力学中心

• 批准号: 10412493
• 负责人: ARTHUR G PALMER
• 金额: $ 184.63万
• 依托单位: NEW YORK STRUCTURAL BIOLOGY CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10412493
• 关键词: Address; Adoption; Automobile Driving; Biological; Biological Process; Biology; Biomedical Technology; Biophysics; Biopolymers; Catalysis; Cell Death; Chemicals; Collaborations; Communities; Community Outreach; Complex; Computational Technique; Computer software; Computers and Advanced Instrumentation; Computing Methodologies; Coupling; Cryoelectron Microscopy; Data Analyses; Degenerative Disorder; Deposition; Development; Education and Outreach; Educational workshop; Ensure; Environment; Equipment; Freezing; Future; Geography; Gills; Health; Human; International; Investigation; Kinetics; Laboratories; Ligands; Link; Malignant Neoplasms; Measurement; Medical; Membrane Proteins; Metabolic Diseases; Methods; Mission; Modernization; Molecular Conformation; NMR Spectroscopy; Nature; New York; Nuclear; Nucleic Acid Conformation; Office of Administrative Management; Pathway interactions; Physiologic pulse; Pilot Projects; Procedures; Process; Production; Property; Proteins; Protocols documentation; Publications; Relaxation; Research; Research Personnel; Resolution; Resources; Scientist; Services; Signal Transduction; Site; Specialist; Strategic Planning; Structure; System; Techniques; Technology; Technology Transfer; Time; Training; Training Activity; Work; X ray diffraction analysis; biological research; cancer cell; community engagement; data acquisition; experimental study; high risk; improved; instrument; instrumentation; macromolecule; magnetic field; novel; pedagogy; pressure; program dissemination; programs; public database; recruit; restraint; solid state nuclear magnetic resonance; structural biology; symposium; synergism; technology development; technology validation; web site

This proposal describes the mission and strategic plans for of a Biomedical Technology Development and Dissemination Center (RM1) entitled Center on Macromolecular Dynamics by NMR Spectroscopy (CoMD/NMR). Located at the New York Structural Biology Center, CoMD/NMR has developed new experimental and computational techniques in NMR spectroscopy, including both structure and dynamics methods for both solution and solid state NMR. Here we focus mainly on spin relaxation methods, which have already had great impact for characterizing protein and nucleic acid conformational dynamics during biological processes including ligand recognition, allosterism, oligomerization, catalysis, and folding. The central challenge addressed by CoMD/NMR is to break down the high activation barrier for new users to apply advanced NMR spectroscopic and computational methods and thereby make sophisticated NMR approaches available to a wide biological research community. To do so, CoMD/NMR addresses four primary obstacles. (i) Because dynamics problems for biopolymers are frequently underdetermined, we develop incisive new experiments, pulse sequences and computational methods. (ii) Because access to advanced NMR instruments can be a limitation for many users, we provide access to a range of enabling NMR instrumentation, including NMR spectrometers at multiple static magnetic fields, a range of modern probes, dynamic nuclear polarization, rapid-freeze-quench, high-pressure equipment, and field cycling relaxometry, all in a well maintained, staff supported, and multiuser environment. (iii) Because transfer of technology to biologists (and even to NMR spectroscopists) has been hindered by the complexity of the methods, and since time efficient use of the instruments is crucial, we develop robust efficient pipelines to facilitate experimental planning, data acquisition and analysis by non- specialists. (iv) Because biologists with research programs that would benefit from these methods are unaware of the potential, we engage in community outreach and education. A unique strength of our program is the integration of forefront solid state NMR, solution NMR and computational experts, and this proposal highlights synergy across these approaches. Additionally, being situated within the NYSBC, we have excellent partnerships with X-ray diffraction, Cryo EM, and membrane protein production technologies. Given the demanding nature of the three Technology Development Projects (TDPs) proposed herein, we have identified a number of Technology Partnership Projects (TPPs), engaging world leaders in aspects of NMR who have indicated their eagerness to partner with us. Technology development proceeds most effectively when driven by exciting and challenging applications; accordingly, CoMD/NMR will work closely with outstanding local and national investigators through Collaborative and Service Projects (CSP), Driving Biomedical Projects (DBB) and Community Engagement (CE) activities, including extensive training and dissemination programs. Through its various components, CoMD/NMR will impact a diverse range of biological research with human health relatedness, including degenerative diseases, metabolic disorders, and cancer.

该提案描述了生物医学技术开发和发展的使命和战略计划 传播中心(RM1)，名为核磁共振波谱大分子动力学中心 (COMD/核磁共振)。位于纽约结构生物学中心的COMD/核磁共振已经开发出新的 核磁共振波谱的实验和计算技术，包括结构和动力学 溶液核磁共振和固体核磁共振的方法。在这里，我们主要关注自旋松弛方法，它有 已经对表征生物过程中的蛋白质和核酸构象动力学产生了巨大的影响 包括配基识别、变构、齐聚、催化和折叠等过程。中环 COMD/核磁共振解决的挑战是打破新用户申请的高激活障碍 先进的核磁共振波谱和计算方法，从而实现复杂的核磁共振方法 可供广泛的生物研究社区使用。要做到这一点，COMD/核磁共振解决了四个主要障碍。 (I)由于生物聚合物的动力学问题经常被低估，我们开发了新的精辟的 实验、脉冲序列和计算方法。 (Ii)由于获得先进的核磁共振仪器对许多用户来说可能是一个限制，因此我们提供 到一系列启用的核磁共振仪器，包括多个静磁的核磁共振谱仪 场，一系列现代探头，动态核极化，快速冷冻-淬火，高压 设备和野外自行车放松测量仪，所有这些都在维护良好、工作人员支持和多用户的情况下进行 环境。 (三)因为向生物学家(甚至向核磁共振光谱仪)转让技术受到以下因素的阻碍 方法的复杂性，而且由于及时有效地使用这些工具是至关重要的，我们开发了 强大高效的管道，以促进实验规划、数据采集和分析 专家。 (Iv)因为拥有将从这些方法中受益的研究计划的生物学家不知道 为了挖掘潜力，我们参与了社区外展和教育。 我们计划的一个独特优势是集成了前沿固态核磁共振、溶液核磁共振和 这项提议突出了这些方法之间的协同作用。此外，作为 位于NYSBC内部，我们与X射线衍射、Cryo EM和薄膜有着良好的合作伙伴关系 蛋白质生产技术。鉴于三个技术开发项目的要求很高 (TDP)，我们已经确定了一些技术合作伙伴项目(TPP)， 核磁共振领域的世界领导人，他们已经表示渴望与我们合作。技术 当由令人兴奋和具有挑战性的应用程序驱动时，开发工作进行得最有效；因此， COMD/核磁共振将与优秀的地方和国家调查人员密切合作，通过合作和 服务项目(CSP)、推动生物医学项目(DBB)和社区参与(CE)活动； 包括广泛的培训和传播计划。通过其各种组件，COMD/核磁共振将 影响与人类健康相关的各种生物学研究，包括退行性疾病， 代谢紊乱和癌症。