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: 10654062
• 负责人: ARTHUR G PALMER
• 金额: $ 157.05万
• 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/10654062
• 关键词: Address; Adoption; Automobile Driving; Biological; Biological Process; Biology; Biomedical Technology; Biophysics; Biopolymers; Catalysis; Cell Death; Chemicals; Collaborations; Communities; Community Health Education; Community Outreach; Complex; Computational Technique; Computer software; Computers and Advanced Instrumentation; Computing Methodologies; Coupling; Cryoelectron Microscopy; Data Analyses; Degenerative Disorder; Deposition; Development; 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; Pathway interactions; Physiologic pulse; Pilot Projects; Procedures; Process; Production; Property; Proteins; Protocols documentation; Publications; Qualifying; Relaxation; Research; Research Personnel; Resolution; Resources; Rotation; 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; community engagement; data acquisition; experimental analysis; experimental study; high risk; improved; instrument; instrumentation; macromolecule; magnetic field; novel; online tutorial; 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.

本提案描述了生物医学技术开发和发展的使命和战略计划

项目成果

Contribution of protein conformational heterogeneity to NMR lineshapes at cryogenic temperatures.

低温下蛋白质构象异质性对 NMR 线形的贡献。

• DOI: 10.1073/pnas.2301053120
• 发表时间: 2024
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Yi,Xu;Fritzsching,KeithJ;Rogawski,Rivkah;Xu,Yunyao;McDermott,AnnE
• 通讯作者: McDermott,AnnE