Acquisition of X-Ray Diffraction Equipment for Macromolecular Crystallography

摘要介绍。x射线结构分析是伊利诺伊大学芝加哥分校（UIC）一大群主要研究人员的关键工具，该团队每年的研究经费目前总计为400万（第三节）。七个实验室参与了十个不同的大分子结构项目，这些项目需要区域探测器技术。现在，为了满足这些基础科学研究项目的许多需求，ucic正在全校范围内努力建立一个综合的、集中的x射线衍射设备。作为这一更大计划的一部分，这项建议是购买最先进的区域探测器和有关的大分子晶体学设备。提出了仪器。从这个提议中采购的设备包括五个主要部分：1)一个旋转阳极x射线发生器，这是现有的最强的内部x射线光子源；2)面积检测器，用于最有效地测量数千个衍射数据；3)低温装置，用于延长辐射敏感样品的寿命；4)一台主机，用于探测器的操作，以及原始数据的采集和处理；5)图形工作站和软件，用于从数据中计算结构，并显示和分析结果。x射线设备的报价和产品信息已经从四个不同的供应商那里收到。虽然详细预算（附录五，p.20）是为某一特定供应商编写的，但其他报价的总额相同。如果签订合同，将在详细的性能比较后确定设备的实际制造和将要采购的区域探测器的类型（荧光屏、成像板、多线）。进行研究和培训。使用拟议的x射线设备进行的研究活动将是分子的三维结构测定。生物大分子的结构将构成大部分的工作。这些包括研究活动部分（第4-11页）中描述的蛋白质晶体学项目。非生物大分子项目（金属簇化合物）需要探测器技术，因为它们的细胞尺寸、溶剂含量和辐射灵敏度与标准蛋白质晶体学工作相媲美。培训对象主要是参与部门的博士研究生。他们研究的结构方面将由具有x射线结构测定专业知识的三名主要研究人员组成的核心人员监督，他们将与感兴趣的实验室密切互动。培训将侧重于x射线结构分析在基础科学研究项目中的应用。计划中的x射线设备的一个重要特征将是它与今年在ucic启动的分子生物学培训计划的关系。该计划包括参与该提案的六个部门中的三个（微生物学与免疫学，生物化学和生理学与生物物理学）。由于x光设备的存在，培训计划的结构生物学部分将大大加强。这一安排将增加结构生物学研究生的潜在人数，从而最大限度地促进x射线设施的利用。由资金引起的活动。UIC的x射线将通过为正在进行的结构项目提供必要的晶体学工具，对我们校园的研究绩效产生重大影响。这将提高我们许多实验室在获得外部机构资金方面的成功率。由于该设施将为我们的多学科基础科学研究小组带来结构分析的重点，它也将促进参与者之间的互动和进一步合作。

ABSTRACT Introduction. X-ray structure analysis is a critical tool for a large group of major researchers at the University of Illinois at Chicago (UIC), a group whose annual research funding currently totals 4 million(Sec III). Seven laboratories are engaged in ten different macromolecular structure projects that require area detector technology. There is now a campus wide effort for establishing a comprehensive, centralized x-ray diffraction facility at UIC to serve the many needs of these basic science research projects. As part of that larger plan, this proposal if for acquisition of a state-of-the-art area detector and related equipment for macromolecular crystallography. Proposed Instrumentation. The equipment to be procured from this proposal consists of five main components: 1) a rotating anode x-ray generator, the strongest in-house source of x-ray photons available; 2) an area detector, for the most efficient measurement of the thousands of diffraction data; 3) a low temperature device, for lifetime extension of the radiation sensitive samples; 4) a host computer, for detector operation, and primary data collection and processing; and 5) a graphics workstation and software, for calculation of structures from the data, and display and analysis of the results. Price quotes and product information for the x-ray equipment have been received from four different suppliers. Although the detailed budget (Appendix V, p.20) is written for one specific supplier, the other quotes are at an equivalent total amount. The actual make of the equipment and type of area detector to be procured (fluorescent screen vs. imaging plate vs. multiwire) will be finalized after detailed performance comparisons if an award is made. Research and Training to be Conducted. The research activities to be conducted with the proposed x-ray equipment will be three-dimensional structural determination of molecules. Structures of biological macromolecules will consti tute the majority of the work. These include the protein crystallography projects described in the research activities section (pp. 4-11) The non-biological macromolecule projects (metallocluster compounds) require are detector technology in that their cell dimensions, solvent content, and radiation sensitivity rival those of standard protein crystallography work. The training will be primarily for doctorate level graduate students from the participating departments. The structural aspects of their research will be supervised by a core of three principal investigators with expertise in x-ray structure determination, who will closely interact with the interested laboratories. The training will concentrate on the application of x-ray structure analysis to their basic science research projects. An important feature of the planned x-ray facility will be in its relationship to the Molecular Biology training program initiated this year at UIC. The program includes three of the six departments participation in this proposal (Microbiology & Immunology, Biochemistry, and Physiology & Biophysics). The structural biology component of the training program will be substantially enhanced by the presence of the x-ray facility. In turn, this arrangement will increase the pool of potential graduate students for structural biology, and thus promote utilization of the x- ray facility to its maximum potential. Activity Resulting from Funding. An x-ray at UIC will have a significant impact on research performance on our campus by providing the necessary crystallographic tools for the ongoing structural projects. This will improve the success rate of our many laboratories in securing external agency funds. Because the facility will bring a focus to structural analysis for our multidisciplinary group of basic science researchers, it will also foster interaction and further collaboration among the participants.