High quality and high throughput Small‐Angle X‐ray Scattering

TOC 2：高质量和高通量小角X射线散射 一个序列规模结构的角度，再加上对这些结构如何变化的理解， 功能是基本的机械洞察生物分子，可以通过结合小 角X射线散射（SAXS）与结构的高分辨率快照。这一战略最近被 随着从序列中精确预测结构的出现，这一点得到了极大的实现。此外，有效 通过SAXS鉴定促进最大结构均一性的条件和构建体， 构象和组装对于捕获高分辨率快照是非常有利的， 显微镜（EM）、大分子X射线晶体学（MX）或核磁共振（NMR）。TOC2 资助的SIBYLS小组在发展一个富有成效的SAXS社区和推进 结构生物学的强大SAXS工具。 通过应用和改进促进计划、调度、执行、分析和分发的管道， 高通量（HT-SAXS）和尺寸排阻耦合（SEC-SAXS）SAXS的结果，SIBYLS正在增加 SAXS被生物医学研究者利用了很多次。SIBYLS光束线的TOC 2探索了一种独特的 收集HT-SAXS数据的平台，对蛋白质工程产生了重要影响。该系统 设计为具有大容量以增加吞吐量。在这次更新过程中，我们将利用 这种能力。TOC 2还根据mail-in/hand-in HT-SAXS模型实施了SEC-SAXS程序 程序. SEC-SAXS最好部署在同步加速器上，因为收集速度与样品洗脱速度相匹配。 SEC-SAXS在瞬态复合物的表征中具有很大的影响。提高效率， 在大流行期间和同步加速器的建立过程中，大部分远程数据收集尤为重要 停工 在接下来的五年里，通过ALS-ENABLE，TOC 2将为以下人员提供高效的SAXS分析访问权限： 数百名生物医学研究人员TOC 2采用的先进技术将产生丰富的数据 这将需要通过结合自动化脚本、在TOC 2中开发的Web应用程序以及 由peers开发。我们将通过ALS-ENABLE利用共享资源和规模经济， 支持高级Web工具的编程，提供严重依赖于强大的计算 组织、处理和存储数据的基础设施。通过贯彻TOC 2目标，ALS-ENABLE将 增加SAXS实验的价值，并在数量上提高可及性-提供质量。

Project Summary TOC2: High quality and high throughput Small Angle X-ray Scattering A sequence scale structural perspective coupled to an understanding of how these structures change during function is fundamental for mechanistic insights into bio-molecules and can be obtained by combining Small Angle X-ray Scattering (SAXS) with high-resolution snapshots of structure. This strategy has been recently been greatly enabled with the advent of accurate structure prediction from sequence. Furthermore, efficiently identifying the conditions and constructs by SAXS that promote the greatest structural homogeneity in conformation and assembly is hugely advantageous to capture a high-resolution snapshot whether from electron microscopy (EM), macromolecular X-ray crystallography (MX) or nuclear magnetic resonance (NMR). The TOC2 funded SIBYLS group has been instrumental in developing a productive SAXS community and advancing powerful SAXS tools for structural biology. By applying and improving a pipeline that promotes planning, scheduling, executing, analyzing and distributing results for for high-throughput (HT-SAXS) and size exclusion coupled (SEC-SAXS) SAXS, SIBYLS is increasing SAXS utilization by biomedical investigators many-fold. TOC2 at the SIBYLS beamline has explored a unique platform for collecting HT-SAXS data that has had an important impact on protein engineering. The system was designed with a large capacity to increase throughput. Over the course of this renewal we will take advantage of this capacity. TOC2 has also implemented an SEC-SAXS program modelled after the mail-in/hand-in HT-SAXS program. SEC-SAXS is best deployed at synchrotrons as the collection speed matches sample elution speed. SEC-SAXS has had a large impact in the characterization of transient complexes. The increased efficiency and largely remote data collection is particularly important during the pandemic and in the build up to synchrotron shutdowns. Over the next five years through ALS-ENABLE, TOC2 will provide efficient access to SAXS analyses for hundreds of biomedical investigators. The advanced technologies TOC2 employs will generate abundant data that will require analysis by a combination of automated scripts, web applications developed in TOC2 and those developed by peers. We will make use of shared resources and an economy of scale through ALS-ENABLE to support programming of advanced web tools delivering a pipeline that relies heavily on a robust computational infrastructure to organize, process, and store data. By following through on TOC2 aims ALS-ENABLE will increase the value of SAXS experiments and increase accessibility – providing quality in quantity.