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.

该建议描述了生物医学技术研究的需求和概述 NMR光谱法（COMD/NMR）的主要分子动力学中心的资源 位于纽约结构生物学中心。 COMD/NMR的重点是技术 NMR自旋松弛和相关方法的开发和应用 蛋白质和核酸构象动力学在包括配体在内的生物学过程 识别，变构，催化和折叠。 COMD/NMR提出的主要挑战 是为了打破使用高级NMR光谱和 计算方法，因此可以提供这些复杂的好处 与更广泛的生物学研究界的方法。 COMD/NMR是开会的平台 通过技术研发（TR＆D）项目的挑战，驾驶 生物医学项目（DBP），协作和服务，培训和传播 资源的组成部分。 COMD/NMR的TR＆D组件将开发新的，并且 表征和解释大分子动力学的扩展方法，具有强大的 专注于扩展时间尺度的一般范围和可访问目标的质量 学习。整合实验，计算和理论方法的双重需求 （在TR＆D组件中）和与关键生物学研究人员（在DBP中）进行接口 和协作组件）使COMD/NMR必不可少。特别是COMD/NMR 解决四个主要障碍：（i）未来的技术发展需要合并 样本准备，NMR硬件和方法开发以及 与计算机方法集成； （ii）在多个静态磁性的情况下访问NMR光谱仪 田地以及专业设备，例如动态核极化和场循环 探针是许多新兴方法的关键。 （iii）将技术转移到一般生物学 社区受到方法的复杂性的阻碍，缺乏综合 促进非专业人士的数据获取和分析的管道，以及缺乏基础设施 单个实验室将这些方法转换为一般用途； （iv）生物学家与 从这些方法中受益的研究计划没有意识到这种潜力，并且缺乏 将这些方法纳入自己的研究中的专业知识。技术发展 受到挑战性应用程序的驱动，最有效地进行；因此，COMD/NMR会 与DBP的杰出当地和国家调查员紧密合作，以激励和 测试新兴技术。 COMD/NMR的资源将广泛使用 生物医学研究社区通过协作和服务活动以及 广泛的培训和传播计划。基础研究的发展 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，代谢性疾病和癌症。

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