THE APPLICATION OF SOLUTION X-RAY SCATTERING TO HIGH-THROUGHPUT STRUCTURAL STUDI

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们建议研究蛋白质目标出现的高通量结构晶体学管道的纯化阶段的解决方案X射线散射。我们的努力将集中在一个子集的结构基因组学目标，成功纯化，但尚未提供结构数据。我们的最终目标是从头获得这些目标的分子包膜，特别是大的蛋白质复合物。通过X射线散射获得的关于四元结构平衡和颗粒间相互作用的额外知识对于细化结晶条件将是非常有价值的。作为对照，还将研究提供结构数据的样本目标，以建立基线。Hauptman-Woodward医学研究所在高通量方法开发方面的经验、>9000个大分子的样品库以及原始计算能力将与SSRL最先进的光束线4-2和96孔、板基、小角度X射线散射专业知识相结合，利用溶液X射线散射作为补充的高通量技术来获得有价值的结构信息。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose to study protein targets emerging out of the purification stage of a high-throughput structural crystallography pipeline by solution x-ray scattering. Our effort will focus on a subset of structural genomics targets that were successfully purified but did not yet provide structural data. Our ultimate goal is to obtain molecular envelopes ab initio for those targets, especially large protein complexes. Additional knowledge obtained on quaternary structure equilibrium and interparticle interaction obtained by x-ray scattering will be highly valuable for refining crystallization conditions. As a control, sample targets that provided structural data will also be studied to establish a baseline. Experience with highthroughput methods development, a sample library of >9000 macromolecules, and raw computing power available at the Hauptman-Woodward Medical Research Institute will be combined with a state-of-the-art beamline 4-2 and 96-well, platebased, small angle X-ray scattering expertise at SSRL to utilize solution x-ray scattering as a complementary, highthroughput technique to obtain valuable structural information.