Data Reduction, Analysis and Modeling pp.619-680

BioCAT生物技术研究资源在Advanced Photon操作X射线束线18ID 资料来源：阿贡国家实验室。现在已经运营了20年，它是一个成熟的、多产的设施， 许多能力在美国是独一无二的，可以说是世界独一无二的。展望未来，我们打算维护我们的世界- 具有光束线增强的静态、时间和空间分辨光纤衍射的一流能力 提高了通量和光束质量。一种新型高速、高灵敏度、高空间分辨率的像素阵列 探测器将提供一个很好的匹配我们的肌肉衍射计划的需求。还提出了一项 可使用两种复合折射透镜之一的多功能微衍射/微小角X射线衍射仪 针对广角或小角度纤维结晶学和连续流动SAXS实验进行了优化。我们会 实现了多峰扫描显微衍射、x射线荧光显微镜、相衬和紫外可见 成像可以单独进行，也可以结合使用同一仪器对相同的样品进行。 时间分辨SAXS的发展将把可用的时间范围从500 ns延长到几秒，主要 与现有能力相比，样品消耗量减少了一个数量级以上。这将允许 需要解决的生物医学问题的范围比以前大得多。一种新的光束线数据 采集和控制系统将为所有用户提供通用接口和更好的数据管理 为时间分辨实验提供实验和高级支持。综合折射率，动态光 用SAXS进行散射和多角度光散射测量将提供更全面的样品 在线表征，以获得更可靠的结果。多尺度建模工作将允许提取更多 来自肌肉X射线衍射研究的信息。在多尺度模拟方面的拟议发展 解释单分子SAXS数据将深刻有助于对多组分体系的研究，这些体系表明 相当大的构象异质性。我们与CCP-SAS项目的关系将使我们能够广泛地 将我们创建的高级建模工具不仅传播给我们所有的DBP、协作和服务用户 而是对更广泛的生物医学界。我们推动的生物医学项目、协作和服务项目 与肌肉功能、心脏病、视网膜色素变性、癌症和 神经退行性疾病。我们建议的培训活动旨在确保安全、高效和 用户对资源的有效利用。我们建议的传播活动旨在扩大我们的 用户社区，使目标生物医学社区充分了解资源能力。

The BioCAT Biotechnology Research Resource operates X-ray beamline 18ID at the Advanced Photon Source, Argonne National Laboratory. Now in its 20th year of operation, it is a mature, productive facility with many capabilities unique in the USA, and, arguably, the world. Going forward, we intend to maintain our world- class capabilities in static, time- and spatially-resolved fiber diffraction with beamline enhancements for increased flux and beam quality. A novel high speed, high sensitivity, high spatial resolution pixel array detector will provide an excellent match to the needs of our muscle diffraction program. Also proposed is a versatile micro-diffraction/micro-SAXS instrument that can use one of two Compound Refractive Lenses optimized for either wide- or small-angle fiber crystallography, and continuous flow SAXS experiments. We will implement multimodal scanning micro-diffraction, x-ray florescence microscopy, phase contrast and uv/visible imaging that can be done either singly or in combination with the same instrument on the same samples. Developments in time-resolved SAXS will extend available time regimes from 500 ns to seconds with major reductions in sample consumption, by more than order of magnitude, from current capabilities. This will allow a much wider range of biomedical problems to be addressed than previously possible. A new beamline data acquisition and control system will provide a common interface and better data management for all experiments and advanced support for time resolved experiments. Combined refractive index, dynamic light scattering and multi-angle light scattering measurements with SAXS will offer more comprehensive sample characterization on-line for more robust results. A multi-scale modeling effort will allow extracting more information from muscle X-ray diffraction studies. The proposed developments in multi-scale simulations for interpreting single molecule SAXS data will profoundly benefit studies of multicomponent systems that show considerable conformational heterogeneity. Our relationship with the CCP-SAS project will enable us to widely disseminate the advanced modeling tools we create to not only all our DBP's, collaborative and service users but to the wider biomedical community. Our Driving Biomedical Projects, collaborative, and service projects have relevance to basic mechanisms of muscle function, heart disease, retinitis pigmentosa, cancer and neuro-degenerative diseases. Our proposed training activities are designed to ensure safe, efficient and productive use of the resource by our users. Our proposed dissemination activities are designed to grow our user community by keeping targeted biomedical communities well-informed of resource capabilities.