A Synchroton Radiation Structural Biology Resource

描述（由申请人提供）：同步辐射（SR）是一种非常明亮和可调的X射线源，可用于结构分子生物学（SMB）的前沿研究。“同步加速器结构生物学资源”由美国国立卫生研究院和能源部在斯坦福大学同步加速器辐射光源（SSRL）提供支持，以开发大分子晶体学、X射线吸收光谱学和小角度X射线散射/衍射方面的新技术，培训/支持用户，并将这些能力传播给生物医学研究界。这 该提案旨在继续为该资源提供资金、运营和未来发展。新的举措将利用SSRL的第三代存储环SPEARS不断提高的SR性能。还建议开发世界上第一台X射线自由电子激光器（LCLS）的选定SMB应用程序，该激光器刚刚开始在SLAC运行。主要目标是优化SSRL的9-i-SMB专用束线（另有两条正在建设中）的实验设施和仪器、探测器、软件和计算性能，以充分利用SPEAR 3在500 mA电流下提供的高亮度。这将使该资源能够通过建立在最先进的仪器和方法、创新软件和自动化/高通量系统基础上的新举措推进科学前沿，用于：研究大型复杂生物分子和分子机器的高分辨率结构/功能;对非晶体生物材料中元素的空间分布和化学性质进行成像;研究生物物理学中的基本问题，如蛋白质和RNA折叠;开发/改进方法，用超快或快速散射和吸收技术研究化学和生物系统中非常快速的时间分辨结构变化。这些科学进步将通过软件的并行开发得到促进，以提供仪器和探测器控制、远程数据收集和实时数据分析的扩展能力。推动涉及大量外部科学家的生物医学项目和合作研究计划将推动和支持核心技术的发展，通过与NCRR CTSA中心的合作，转化研究的步伐将加快，并且在培训和传播方面的高度活跃的计划将把它们带到广泛的用户社区。 公共卫生相关性：相关性是一些重要的生物学问题，包括酶，金属蛋白质，膜结合蛋白质和免疫球蛋白的结构;参与代谢和光合作用的金属蛋白质的活性部位结构;以及这些结构如何在不同状态下变化或随着反应或事件如蛋白质折叠或构象变化发生而演变。这些信息对药物设计、癌症研究和病毒学等与健康相关的领域更为重要。

DESCRIPTION (provided by applicant): Synchrotron radiation (SR) is an extremely bright and tunable x-ray source that enables forefront research in Structural molecular biology (SMB). A "Synchrotron Structural Biology Resource" is supported at the Stanford Synchrotron Radiation Lightsource (SSRL) by the NIH and DOE to develop new technologies in macromolecular crystallography, x-ray absorption spectroscopy and small angle x-ray scattering/diffraction, to train/support users, and to disseminate these capabilities to the biomedical research community. This proposal is for the continued funding, operation and future development of this Resource. New initiatives will capitalize on the increasing SR performance of SSRL's 3'" generation storage ring SPEARS. Proposed also is the development of selected SMB applications of the world's first x-ray free-electron laser (LCLS), just beginning operation at SLAC. A principal aim is to optimize experimental facilities and instrumentation, detectors, software and compute performance on the 9-i- SMB dedicated beam lines at SSRL (with another two in construction) to take full advantage of the high brightness provided by SPEAR3 at 500 mA current. This will enable the Resource to advance the scientific forefront with new initiatives built upon state-of-the-art instrumentation and methodologies, innovative software and automated/high-throughput systems for: studying high resolution structures/function of large, complex biomolecules and molecular machines; imaging the spatial distribution and chemical nature of elements in non-crystalline biological materials; investigating fundamental questions in biophysics such as protein and RNA folding; and developing/improving methods for studying very fast time-resolved structural changes in chemical and biological systems with ultrafast or fast scattering and absorption techniques. These scientific advancements will be facilitated by parallel developments in software to provide expanded capabilities for instrument and detector control, remote data collection and real-time data analysis. Driving biomedical projects and collaborative research programs involving a large number of outside scientists will drive and support core technological developments, the pace of translational research will be accelerated through collaborations with NCRR CTSA Centers, and a highly active program in training and dissemination will bring them to a wide user community. PUBLIC HEALTH RELEVANCE: Relevance is to a number of important biological problems including the structure of enzymes, metalloproteins, membrane-bound proteins and immunoglobulins; the active site structure of metalloproteins involved in metabolism and photosynthesis; and how these structures change in different states or evolve in time as reactions or events like protein folding or conformational changes occur. Such information is more broadly important to the health-related areas of drug design, cancer research, and virology.