Beamline Automation for Structure Determination

描述（由申请人提供）：该提案旨在申请资助GM 62648的竞争性更新，以进一步开发生物分子X射线晶体学的工具和自动化。这些工具对结构生物学界具有广泛的益处，因为它们提供了改进和优化的X射线数据收集和处理方法，以及研究人员与同步加速器晶体学光束线上的复杂仪器互动的改进和新方法。同步加速器光束线为结构生物学提供了大部分X射线数据，并使人们能够追求更具挑战性的结构项目，如核糖体，RNA聚合酶复合物和膜蛋白。高度自动化的技术和方法的开发对于科学界的生产力至关重要，并且对于提高结构基因组学和药物发现项目的高通量能力是必要的。在过去的四年里，我们设计、实施和测试了一个自动化晶体安装和对准系统，将其集成到先进光源的第5区光束线控制系统中，根据测试和用户反馈进行了广泛的测试和改进，开始与Paul亚当斯（LBNL）团队合作，以实现更全面的自动化数据收集和处理，并开始了该系统向其他同步加速器光束线的协作传播。对于这次更新，我们建议重点关注以下目标：1）升级自动化样品处理系统的设计-完成第一代系统的硬件和夹持器组件的改进，以及设计、实施和测试具有卡环几何结构的第二代系统; 2）改进晶体识别和对准并使其更加自动化; 3）改进样品跟踪子系统并使其更加自动化; 4）发展用户指导的远程测量和信息管理能力。这些技术可推广到其他网站和广泛的用户需求。

DESCRIPTION (provided by applicant): This proposal is to request funding for a competing renewal of GM62648 to further develop tools and automation for x-ray crystallography of biological molecules. These tools have wide benefit to the structural biology community as they provide improved and optimized approaches to x-ray data collection and processing, as well as improvements and new methods for researchers to interact with the complex instrumentation at synchrotron crystallography beamlines. The synchrotron beamlines provide the majority of x-ray data for structural biology, and enable the pursuit of ever more challenging structural projects such as the ribosome, RNA polymerase complexes, and integral membrane proteins. The development of highly-automated technologies and methods is critical to the productivity of the scientific community and is necessary to increase the high- throughput capabilities for structural genomics and drug discovery projects. Over the past four years, we have designed, implemented, and tested an automated crystal mounting and alignment system, integrated it into the beamline control system in sector 5 at the Advanced Light Source, extensively tested and improved it in response to the tests and user feedback, started an effort with the group of Paul Adams (LBNL) to more fully automate data collection and processing, and begun the collaborative propagation of the system to other synchrotron beamlines. For this renewal, we propose to focus on the following goals: 1) Upgrade of the design of the automated sample- handling system - finalizing hardware of first generation system and improvements in the gripper assembly, and the design, implement, and testing second-generation system with cartesian geometry; 2) Improve and more fully automate crystal recognition and alignment; 3) Improve and more fully automate the sample-tracking subsystem; 4) Develop a user-directed remote measurement and information management capability. These technologies are generalizable to the other sites and to a broad range of user needs.