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

TOC2项目概要：高质量和高通量小角X射线散射 序列尺度结构透视，结合对这些结构如何在 功能是对生物分子的机械洞察的基础，可以通过将小分子 具有高分辨率结构快照的角度X射线散射(SAXS)。这一战略最近一直在 随着从序列中进行准确的结构预测的出现，极大地实现了这一点。此外，高效地 通过SAXS确定促进最大结构同质性的条件和结构 构象和组装对于捕捉高分辨率的快照是非常有利的，无论是从电子 显微镜(EM)、大分子X射线结晶学(MX)或核磁共振(核磁共振)。TOC2 资助的SIBYLS小组在开发富有成效的SAXS社区和推动 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、分析和分配的流水线 对于高吞吐量(HT-SAXS)和尺寸排除耦合(SEC-SAXS)SAXS，SIBYLS的结果正在增加 生物医学研究人员对SAXS的使用率提高了许多倍。位于SIBYLS光束线的TOC2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。这个系统是 采用大容量设计，可提高吞吐量。在这次更新过程中，我们将利用 这种能力。TOC2还实施了一项仿照邮寄/交接HT-SAXS的SEC-SAXS计划 程序。SEC-SAXS最好部署在同步加速器上，因为采集速度与样品洗脱速度相匹配。 SEC-SAXS在表征暂态络合物方面有很大的影响。提高的效率和 在疫情大流行期间和在同步加速器的建设过程中，远程数据收集尤其重要 关门。 在接下来的五年里，通过ALS-Enable，TOC2将提供对SAXS分析的高效访问 数以百计的生物医学研究人员。TOC2采用的先进技术将产生丰富的数据 这将需要通过自动脚本、用TOC2开发的Web应用程序和那些 由同行开发。我们将通过ALS利用共享资源和规模经济-使 支持高级Web工具的编程，以交付在很大程度上依赖强大计算的管道 用于组织、处理和存储数据的基础设施。通过贯彻TOC2目标，实现ALS-Enable Will 增加SAXS实验的价值，并在数量上提高可访问性-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.