Center on Macromolecular Dynamics by NMR Spectroscopy

本提案描述了对生物医学技术研究资源的需求和概要 名为核磁共振大分子动力学中心(COMD/核磁共振)，位于新的 约克结构生物学中心。COMD/核磁共振的重点是核磁共振技术的发展和应用 蛋白质和核酸构象动力学的自旋驰豫及其相关表征方法 生物过程包括配基识别、变构、催化和折叠。核心挑战 COMD/核磁共振解决的问题是打破使用先进核磁共振波谱的高活化势垒 和计算方法，从而使这些复杂的方法的好处可用 更广泛的生物研究社区。COMD/核磁共振是通过以下方式迎接这一挑战的平台 技术研发(TR&D)项目，推动生物医学项目(DBP)，协作 以及资源的服务、培训和传播部分。COMD/核磁共振的研发成分 将开发新的和扩展的方法来表征和解释大分子动力学，具有 高度重视扩大可供研究的时间尺度和对象的一般范围。双重奏 需要整合实验、计算和理论方法(在研发部门内)和 与关键的生物学研究人员(在DBP和协作组件内)进行交互 COMD/核磁共振是必需的。特别是，COMD/核磁共振解决了四个主要障碍：(1)未来技术 发展需要在样品制备、核磁共振硬件和方法开发方面取得综合进展， 以及与计算机方法的集成；(Ii)在多个静态磁场下访问核磁共振光谱仪，如 以及动态核极化和场循环探测器等特殊设备，是许多 新出现的方法；(3)向一般生物界转让技术受到 方法复杂，缺乏综合管道来促进非政府组织的数据采集和分析 专家，个别实验室缺乏将这些方法转化为普遍使用的基础设施；以及 (4)拥有将从这些方法中受益的研究计划的生物学家没有意识到这种潜力，并且 缺乏将这些方法纳入他们自己的研究的专业知识。技术开发进展最快 在受到具有挑战性的应用程序的驱动时有效；因此，COMD/核磁共振将与 在旨在激励和测试新兴技术的DBP方面，杰出的地方和国家调查人员。这个 COMD/核磁共振资源将通过以下方式广泛提供给生物医学研究界 协作和服务活动，以及广泛的培训和传播计划。最基本的 COMD/核磁共振的研究进展将对人类健康的各种生物学研究产生影响 关联性，包括退行性疾病、代谢紊乱和癌症。

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 non- specialists, 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.