Center on Macromolecular Dynamics by NMR Spectroscopy

核磁共振波谱大分子动力学中心

• 批准号: 10400388
• 负责人: ARTHUR G PALMER
• 金额: $ 47.54万
• 依托单位: NEW YORK STRUCTURAL BIOLOGY CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10400388
• 关键词: Address; Automobile Driving; Basic Science; Biological; Biological Process; Biomedical Research; Biomedical Technology; Catalysis; Collaborations; Communities; Computing Methodologies; Data Analyses; Degenerative Disorder; Development; Emerging Technologies; Equipment; Future; Health; Human; Individual; Infrastructure; Laboratories; Ligands; Malignant Neoplasms; Metabolic Diseases; Methods; NMR Spectroscopy; New York; Nuclear; Nucleic Acid Conformation; Preparation; Proteins; Relaxation; Research; Research Personnel; Resources; Sampling; Services; Technology Transfer; Testing; Time; Training; Translating; Work; biological research; data acquisition; design; magnetic field; medical specialties; meetings; method development; program dissemination; programs; research and development; structural biology; technology development; technology research and development

This proposal describes the need for and outline of a Biomedical Technology Research Resource entitled Center on Macromolecular Dynamics by NMR Spectroscopy (CoMD/NMR) and situated at the New York Structural Biology Center. The focus of CoMD/NMR is technical development and application of NMR spin relaxation and associated methods for characterizing protein and nucleic acid conformational dynamics in biological processes including ligand recognition, allosterism, catalysis, and folding. The central challenge addressed by CoMD/NMR is to break down the high activation barrier to using advanced NMR spectroscopic and computational methods and thus to make available the benefits of these sophisticated approaches to the wider biological research community. CoMD/NMR is the platform for meeting this challenge through Technological Research and Development (TR&D) Projects, Driving Biomedical Projects (DBPs), Collaboration and Service, Training, and Dissemination components of the Resource. The TR&D component of CoMD/NMR will develop new and extended methods for characterizing and interpreting macromolecular dynamics, with a strong focus on expanding the general ranges of time scales and masses of targets accessible for study. The dual needs for integrating experimental, computational, and theoretical methods (within the TR&D component) and for interfacing with key biological researchers (within the DBP and Collaboration components) make CoMD/NMR essential. In particular, CoMD/NMR addresses four primary obstacles: (i) future technology developments requires combined advances in sample preparation, NMR hardware and methods development, and integration with computer methods; (ii) access to NMR spectrometers at multiple static magnetic fields, as well as specialty equipment such as dynamic nuclear polarization and field cycling probes, is key to many emerging methods; (iii) transfer of technology to the general biological community has been hindered by the complexity of the methods, absence of integrated pipelines to facilitate data acquisition and analysis by nonspecialists, and lack of infrastructure in individual laboratories to translate these methods for general use; and (iv) biologists with research programs that would benefit from these methods are unaware of this potential and lack expertise to incorporate these approaches into their own research. Technology development proceeds most effectively when driven by challenging applications; accordingly, CoMD/NMR will work closely with outstanding local and national investigators in DBPs designed to motivate and test emerging technology. The resources of CoMD/NMR will be broadly available to the biomedical research community through collaboration and service activities together with expansive training and dissemination programs. The basic research developments of 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研究的必要性和大纲 核磁共振波谱学大分子动力学中心（Center on Macromolecular Dynamics by NMR Spectroscopy，CoMD/NMR） 位于纽约结构生物学中心。CoMD/NMR的重点是技术 核磁共振自旋弛豫及其表征方法的发展和应用 生物过程中的蛋白质和核酸构象动力学 识别、变构、催化和折叠。CoMD/NMR解决的核心挑战 是打破高活化障碍，使用先进的核磁共振光谱， 计算方法，从而使这些复杂的好处 更广泛的生物研究社区的方法。CoMD/NMR是会议的平台 通过技术研究与开发（TR&D）项目、驾驶来应对这一挑战 生物医学项目（DBP），合作和服务，培训和传播 资源的组成部分。CoMD/NMR的TR&D组件将开发新的， 用于表征和解释大分子动力学的扩展方法，具有强大的 重点是扩大可达到的时间尺度和目标质量的一般范围， study.对整合实验、计算和理论方法的双重需求 （在TR&D组件内）和与关键生物研究人员的接口（在DBP内） 和协作组件）使CoMD/NMR必不可少。特别是，CoMD/NMR 解决了四个主要障碍：（一）未来的技术发展需要结合 样品制备、NMR硬件和方法开发方面的进展，以及 与计算机方法的集成;（二）在多个静态磁场下使用NMR光谱仪 以及专用设备，如动态核极化和场循环 （iii）将技术转让给一般生物技术， 社区一直受到阻碍的复杂性的方法，缺乏综合 管道，以方便非专业人员的数据采集和分析，以及缺乏基础设施， 个别实验室翻译这些方法供一般使用;及（iv）生物学家， 从这些方法中受益的研究项目没有意识到这种潜力， 将这些方法融入自己的研究中。技术开发 当受到挑战性应用的驱动时，CoMD/NMR将最有效地进行;因此， 与优秀的地方和国家DBPs研究人员密切合作， 测试新兴技术。CoMD/NMR的资源将广泛提供给 生物医学研究社区通过合作和服务活动， 广泛的培训和传播方案。基础研究进展 CoMD/NMR将影响与人类健康相关的各种生物学研究， 包括变性疾病、代谢紊乱和癌症。

项目成果

TmDOTP: An NMR-based thermometer for magic angle spinning NMR experiments.

TmDOTP：一种基于 NMR 的温度计，用于魔角旋转 NMR 实验。

• DOI: 10.1016/j.jmr.2019.106574
• 发表时间: 2019
• 期刊: Journal of magnetic resonance (San Diego, Calif. : 1997)
• 作者: Zhang,Dongyu;Itin,Boris;McDermott,AnnE
• 通讯作者: McDermott,AnnE

RING NMR dynamics: software for analysis of multiple NMR relaxation experiments.

• DOI: 10.1007/s10858-020-00350-w
• 发表时间: 2021-01
• 期刊: Journal of biomolecular NMR
• 影响因子: 2.7
• 作者: Beckwith MA;Erazo-Colon T;Johnson BA
• 通讯作者: Johnson BA

Structure and DNA-bridging activity of the essential Rec114-Mei4 trimer interface.

• DOI: 10.1101/gad.350461.123
• 发表时间: 2023-06-01
• 期刊: GENES & DEVELOPMENT
• 影响因子: 10.5
• 作者: Liu, Kaixian;Grasso, Emily M.;Pu, Stephen;Zou, Mengyang;Liu, Shixin;Eliezer, David;Keeney, Scott
• 通讯作者: Keeney, Scott

Informing NMR experiments with molecular dynamics simulations to characterize the dominant activated state of the KcsA ion channel.

• DOI: 10.1063/5.0040649
• 发表时间: 2021-04-28
• 期刊: The Journal of chemical physics

Probing allosteric coupling in a constitutively open mutant of the ion channel KcsA using solid-state NMR.

使用固态 NMR 探测离子通道 KcsA 的组成型开放突变体中的变构耦合。

• DOI: 10.1073/pnas.1908828117
• 发表时间: 2020
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Sun,Zhiyu;Xu,Yunyao;Zhang,Dongyu;McDermott,AnnE
• 通讯作者: McDermott,AnnE