Center on Macromolecular Dynamics by NMR Spectroscopy

本提案描述了生物医学技术研究的必要性和概要 题为用核磁共振波谱研究大分子动力学中心的资源(COMD/核磁共振) 位于纽约结构生物学中心。COMD/核磁共振的重点是技术 核磁共振自旋弛豫及相关表征方法的发展和应用 包括配基在内的生物过程中蛋白质和核酸的构象动力学 识别、变构、催化和折叠。COMD/核磁共振应对的中心挑战 是打破使用先进的核磁共振波谱和 计算方法，从而使这些复杂的 与更广泛的生物研究界接触的方法。COMD/核磁共振是会议的平台 这一挑战通过技术研究和开发(TR&D)项目，推动 生物医学项目(DBP)、协作和服务、培训和传播 资源的组件。COMD/核磁共振的研发部分将开发出新的和 描述和解释大分子动力学的扩展方法，具有很强的 重点扩大时间尺度的一般范围和可获得的目标数量 学习。整合实验、计算和理论方法的双重需要 (在研发部门内)并与关键的生物学研究人员(在DBP内)建立联系 和协作组件)使得COMD/核磁共振必不可少。特别是，COMD/核磁共振 解决四个主要障碍：(1)未来的技术发展需要综合 样品制备、核磁共振硬件和方法开发方面的进展 与计算机方法相结合；(Ii)使用多个静磁的核磁共振谱仪 田野以及特殊设备，如动态核极化和田野自行车 探测是许多新兴方法的关键；(3)向普通生物学转让技术 社区一直受阻于方法的复杂性，缺乏整体性 便利非专业人员获取和分析数据的管道，以及缺乏基础设施 个别实验室将这些方法翻译成通用方法；以及(Iv)生物学家与 将从这些方法中受益的研究项目没有意识到这种潜力和缺乏 将这些方法纳入他们自己的研究中的专业知识。技术发展 当受到具有挑战性的应用程序的驱动时，收益最高效；相应地，COMD/核磁共振将 与当地和国家的优秀调查人员密切合作，旨在激励和 测试新兴技术。COMD/核磁共振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 广泛的培训和传播计划。生物多样性的基础研究进展 COMD/核磁共振将影响与人类健康相关的各种生物学研究， 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 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.