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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们建议用溶液x射线散射法研究高通量结构结晶学管道净化阶段出现的蛋白质靶标。我们的努力将集中在成功纯化但尚未提供结构数据的结构基因组学靶点的子集上。我们的最终目标是从从头开始获得这些靶标的分子包膜，特别是大型蛋白质复合体。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更多知识将对改进结晶条件具有很高的价值。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、&gt；9000大分子的样本库和原始计算能力将与SSRL最先进的光束线4-2和96孔平板小角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，以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.