SOLUTION X-RAY SCATTERING OF DEACTIVATED VIRUS PARTICLES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 在Hauptman-Woodward医学研究所（HWI），我们一直在开发一个由三部分组成的过程，以实现中等通量的病毒结构研究。这包括：1）全病毒颗粒的灭活，2）结晶和自动封装封固，以及3）在环境条件下的高通量同步加速器数据收集。我们建议通过对灭活病毒颗粒进行SAXS实验来表征它们，建立低分辨率分子包膜，并将它们作为生化条件的函数（结晶的前体和有用的指南）来补充这种晶体学方法。高通量方法开发的经验，专门从事病毒灭活和纯化的工业合作者，以及Hauptman-Woodward医学研究所的原始计算能力将与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。我们将利用溶液X射线散射作为一种补充技术，以帮助我们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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. At the Hauptman-Woodward Medical Research Institute (HWI) we have been developing a three part process to enable medium-throughput virus structural studies. This includes; 1) the deactivation of whole virus particles, 2) crystallization and automated encapsulated mounting and, 3) high-throughput synchrotron data collection at ambient conditions. We propose to complement this crystallographic focused approach by conducting SAXS experiments on deactivated virus particles to characterize them, establish low resolution molecular envelopes, and profile them as a function of biochemical conditions (a precursor and useful guide to crystallization). Experience with high-throughput methods development, an industrial collaborator specializing in virus deactivation and purification, 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. We will utilize solution x-ray scattering as a complementary, technique to aid us in obtaining valuable structural information.