A Synchroton Radiation Structural Biology Resource

同步辐射（SR）是一种非常明亮和可调的x射线源，使结构分子生物学（SMB）的前沿研究成为可能。美国国立卫生研究院（NIH）和美国能源部（DOE）在斯坦福同步辐射光源（SSRL）支持“同步加速器结构生物学资源”，以开发大分子晶体学、x射线吸收光谱和小角度x射线散射/衍射等新技术，培训/支持用户，并将这些能力传播给生物医学研究界。这项建议是为了继续资助、运作和未来发展这一资源。新的计划将利用SSRL第三代存储环SPEARS不断提高的SR性能。此外，还提议开发世界上第一台x射线自由电子激光器（LCLS）的SMB应用，该激光器刚刚开始在SLAC运行。主要目的是优化SSRL的9+ SMB专用光束线上的实验设施和仪器，探测器，软件和计算性能（另外两个正在建设中），以充分利用SPEAR3在500 mA电流下提供的高亮度。这将使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/高通量系统上的新举措来推进科学前沿：研究大型，复杂分子和分子机器的高分辨率结构/功能；非晶态生物材料中元素的空间分布和化学性质成像研究生物物理学中的基本问题，如蛋白质和RNA折叠；利用超快或快速散射和吸收技术开发/改进研究化学和生物系统中非常快速的时间分辨结构变化的方法。这些科学进步将通过软件的并行开发来促进，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。推动生物医学项目和涉及大量外部科学家的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，一个高度活跃的培训和传播计划将把它们带到广泛的用户社区。

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 3rd 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+ 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 blomolecules 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.