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.

该建议描述了生物医学技术开发的使命和战略计划 NMR光谱法的传播中心（RM1）标题为大分子动力学中心 （COMD/NMR）。 COMD/NMR位于纽约结构生物学中心，开发了新的 NMR光谱中的实验和计算技术，包括结构和动力学 解决方案和固态NMR的方法。在这里，我们主要关注的是旋转放松方法， 在生物学期间表征蛋白质和核酸构象动力学的影响很大 包括配体识别，变构，寡聚，催化和折叠的过程。中央 COMD/NMR解决的挑战是打破新用户申请的高激活障碍 先进的NMR光谱和计算方法，从而使NMR进行复杂的方法 可用于广泛的生物学研究界。为此，COMD/NMR解决了四个主要障碍。 （i）由于生物聚合物的动态问题经常不确定，因此我们会发展出敏锐的新 实验，脉冲序列和计算方法。 （ii）由于访问高级NMR仪器可能是许多用户的限制，因此我们提供访问权限 到启用NMR仪器的范围，包括多个静态磁性的NMR光谱仪 田地，一系列现代探针，动态核极化，快速冻结，高压 设备和野外循环松弛计，都在维护良好的工作人员中，并且多余 环境。 （iii）由于将技术转移给生物学家（甚至是NMR光谱学家），因此受到了阻碍 这些方法的复杂性以及由于仪器的时间效率使用至关重要，我们会发展 强大的有效管道，以促进实验计划，数据获取和分析 专家。 （iv）由于具有从这些方法中受益的研究计划的生物学家不知道 潜力，我们从事社区外展和教育。 我们程序的独特优势是最前沿固态NMR，解决方案NMR和 计算专家以及该提案强调了这些方法的协同作用。另外，存在 位于NYSBC内，我们与X射线衍射，冷冻EM和膜建立了良好的合作伙伴关系 蛋白质生产技术。考虑到三个技术开发项目的苛刻性质 （TDP）本文提出的，我们已经确定了许多技术伙伴关系项目（TPPS），引人入胜 NMR方面的世界领导人表示渴望与我们合作。技术 在受到激动人心和具有挑战性的应用程序的驱动下，开发进行最有效的行动；因此， COMD/NMR将通过合作和 服务项目（CSP），驾驶生物医学项目（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/NMR将 影响各种各样的生物学研究与人类健康相关性，包括退化性疾病， 代谢疾病和癌症。