Center on Macromolecular Dynamics by NMR Spectroscopy

本提案描述了生物医学技术研究资源的需求和概述 名称为核磁共振光谱法大分子动力学中心（CoMD/NMR），位于纽约 约克结构生物学中心。CoMD/NMR的研究重点是NMR的技术开发和应用 用于表征蛋白质和核酸构象动力学自旋弛豫和相关方法 生物过程包括配体识别、变构、催化和折叠。的主要挑战 通过CoMD/NMR解决的是打破高活化障碍，使用先进的NMR光谱 和计算方法，从而使这些复杂的方法的好处， 更广泛的生物研究社区。CoMD/NMR是应对这一挑战的平台， 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/NMR的TR&D组件 将开发新的和扩展的方法来表征和解释大分子动力学， 重点是扩大可供研究的时间尺度和目标数量的一般范围。双 需要整合实验，计算和理论方法（在TR&D组件内）， 与关键生物学研究人员（DBP和协作组件内）进行交互， CoMD/NMR基本。特别是，CoMD/NMR解决了四个主要障碍：（i）未来技术 发展需要在样品制备、NMR硬件和方法开发方面的综合进步， （ii）在多个静磁场下使用核磁共振波谱仪， 以及专用设备，如动态核极化和场循环探针，是许多关键 （三）技术转让给一般生物界受到阻碍， 方法的复杂性，缺乏综合管道，以方便非 专家，个别实验室缺乏将这些方法转化为一般用途的基础设施; (iv)生物学家的研究计划，将受益于这些方法是不知道这种潜力， 缺乏将这些方法纳入自己研究的专业知识。技术开发收益最大 有效地驱动时，具有挑战性的应用程序;因此，CoMD/NMR将密切合作， 优秀的地方和国家DBPs调查员，旨在激励和测试新兴技术。的 CoMD/NMR的资源将通过以下方式广泛提供给生物医学研究界： 合作和服务活动以及广泛的培训和传播计划。基本 CoMD/NMR的研究进展将影响多种生物学研究与人类健康 相关性，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.