R-axis IV++ Detector and Vari-Max Optics for X-ray Crystallographic Studies

描述（由申请人提供）：本提案要求资金用于购买R-Axis IV++探测器，VariMax高分辨率（HR）光学系统，左端口快门配置，加上外围支持仪器（包括x流冷冻冷却系统），以及将该设备集成到佛罗里达大学（UF）现有大分子x射线衍射数据收集设施所需的必要软件。扩建和改进现有设施（包含Rigaku RUH3R x射线发生器和右端口快门配置，带有Max-Flux（蓝色）共聚焦光学和R-Axis IV++图像板系统）的请求来自以下考虑。首先，在左端口快门上增加第二个带有VariMax HR光学系统的探测器，将使具有大单位细胞（如病毒）的小晶体能够实现真实的内部衍射质量筛选，通过将暴露时间减少到当前系统所需的25%，并使病毒样品的晶体学研究能够在政府机构法规（如美国农业部）下进行，这使得运输非常困难。升级到x流冷冻冷却系统还将消除在长时间数据收集运行期间确保液氮持续供应的需要。此外，由于越来越多的研究小组采用结构生物学工具作为UF生物医学研究项目的组成部分，目前设施的右端口配置的使用接近满负荷。在现有x射线发生器的左端口安装一个额外的R-Axis IV++探测器，将有效地将x射线衍射数据收集设施的可用访问时间增加一倍，用于UF大分子结构测定的研究。这项技术的升级将使NIH pi能够利用x射线晶体学扩展其对生物系统（包括ssDNA病毒、HIV蛋白酶、金属酶和与肿瘤发生、心脏病、免疫系统调节等相关的蛋白质）的结构-功能研究。值得注意的是，这些研究工作旨在开发人类疾病的治疗方法，并以小有机分子、肽抑制剂、疫苗、病毒组装干扰物和基因治疗载体的形式控制病原体。公共卫生相关性：本项目建议扩建佛罗里达大学现有的大分子x射线衍射数据收集设施。所要求的仪器将加强UF NIH研究人员之间正在进行的合作努力，对他们来说，分子表征是他们生物医学研究计划的基础。这些项目旨在开发各种人类疾病的治疗方法，并以小有机分子、肽抑制剂、疫苗、病毒组装干扰物和基因治疗载体的形式控制病原体。

DESCRIPTION (provided by applicant): This proposal requests funds for the purchase of an R-Axis IV++ detector, VariMax High resolution (HR) optical system, and Left port shutter configuration, plus the peripheral support instrumentation (including an X-stream cryo-cooling system), and necessary software required for this equipment to be integrated into the existing macromolecular X-ray diffraction data collection facility at the University of Florida (UF). This request to expand and improve the current facility (which contains a Rigaku RUH3R X-ray generator and Right port shutter configuration with Max-Flux (blue) Confocal optics and R-Axis IV++ Image plate system) comes from the following considerations. Primarily, adding a second detector to the Left port shutter with a VariMax HR optical system will enable realistic in-house diffraction quality screening on small crystals with large unit cells (such as viruses), by reducing exposures times to ~25% of that required on the current system and enabling crystallographic studies of viral samples under government agency regulations (such as USDA) that make transportation very difficult. The upgrade to an X-stream cryo-cooling system will also eliminate the need for insuring constant supplies of liquid nitrogen during long data collection runs. In addition, the usage of the current facility's Right port configuration is at near full capacity, due to the growing number of research groups employing structural biology tools as components of their biomedical research programs at UF. The installation of an additional R-Axis IV++ detector on the Left port of the current X-ray generator will effectively double the amount of available access time to the X-ray diffraction data collection facility for research aimed at macromolecular structure determinations at UF. This upgrade in technology will enable NIH PIs to expand their structure-function studies on biological systems (including ssDNA viruses, HIV proteases, metalloenzymes, and proteins associated with tumorgenesis, heart disease, the modulation of the immune system, and others) using X-ray crystallography. Significantly, these research efforts are directed towards the development of therapeutic treatments of human diseases and the control of pathogens in the form of small organic molecules, peptide inhibitors, vaccines, virus assembly disrupters, and gene therapy vectors. PUBLIC HEALTH RELEVANCE: This project proposes the expansion of the existing macromolecular X-ray diffraction data collection facility at the University of Florida (UF). The requested instrumentation will strengthen ongoing collaborative efforts between UF NIH investigators for whom molecular characterizations form the basis of their biomedical research programs. These projects are aimed at the development of therapeutic treatments of myriad of human disease and the control of pathogens in the form of small organic molecules, peptide inhibitors, vaccines, virus assembly disrupters, and gene therapy vectors.