Upgrade of a Core Laboratory Macromolecular X-ray Diffraction System

核心实验室高分子X射线衍射系统升级

• 批准号: 10176983
• 负责人: Alexander B Taylor
• 金额: $ 43.85万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10176983
• 关键词: Anodes; Applications Grants; Area; Automobile Driving; Businesses; Cancer Biology; Cancer Center; Charge; Communicable Diseases; Coupled; Crystallization; DNA Repair; Data; Data Collection; Data Set; Devices; Drug Design; Generations; Health; Health Sciences; Hour; Human; Image; Institution; Laboratories; Manufacturer Name; Molecular Structure; Names; Natural Immunity; Noise; Optics; Phase; Recording of previous events; Research; Research Personnel; Resolution; Resource Sharing; Resources; Roentgen Rays; Services; Speed; Structural Biochemistry; Structure; System; Technology; Texas; Universities; X ray diffraction analysis; X-Ray Crystallography; detector; drug discovery; drug structure; improved; instrumentation; macromolecule; medical schools; operation; photon-counting detector; structural biology

Project Summary The aim of this Shared Instrumentation Grant proposal is to enhance capabilities for macromolecular X- ray crystallography at the University of Texas Health Science Center at San Antonio (UT Health) X-ray Crystallography Core Laboratory (XRC), located in the Department of Biochemistry & Structural Biology within the Joe R. and Teresa Lozano Long School of Medicine. The XRC has a 20-year history and is an Institutional Research Core under the Office of the Vice President for Research and part of the Drug Discovery & Structural Biology Shared Resource under the NCI-designated Mays Cancer Center. It provides crystallization, X- ray diffraction data collection and macromolecular structure determination services for a wide variety of projects throughout the institution, its centers and the San Antonio area. Users for the instrumentation are investigators for topics such as cancer biology, DNA damage and repair, innate immunity, infectious disease, and drug design to name a few. Current resources in the XRC include a MicroMax 007HF X-ray generator driving two ports with VariMax-HR and HF confocal optics aimed at two mounted R-AXIS HTC imaging plate detectors. The 007HF rotating anode generator has faithfully served XRC users and will be functional and supported for years to come by the manufacturer Rigaku (in business since 1951). However, the imaging plate detectors have been phased out by Rigaku and are no longer eligible for parts support beginning this year. To both continue and enhance XRC operation, we propose to upgrade/replace the two detectors and optics with a single HyPix- 6000HE photon counting detector mounted on a Universal Kappa Goniometer and a VariMax VHF confocal microfocus optic with a continuously adjustable divergence slit assembly. The new instrumentation will be mounted on the existing X-ray generator, taking the place of both obsolete imaging plate systems, and will also use the existing Oxford Cryostream 800 cooling system. The imaging plate technology is two generations behind in technology, superseded by charge coupled device (CCD) detectors and now photon counting detectors. The HyPix-6000HE significantly outperforms imaging plate technology and improves upon CCD technology in that photon counting detectors have high sensitivity and dynamic range while eliminating error due to readout noise and dark current. Additional major advantages are the speed and volume of data that can be acquired by photon counting detectors over our imaging plates. The HyPix-6000HE can acquire full datasets in the timescale of minutes to hours while the image plates require hours to days. Overall, the requested upgrade to the XRC will benefit investigators with rapid, high quality, high resolution data collection to accomplish structure determinations of macromolecules relevant to human health in short order.

项目摘要 该共享仪器赠款提案的目的是增强大分子X-的能力 圣安东尼奥（UT Health）X射线的德克萨斯大学健康科学中心的射线晶体学 晶体学核心实验室（XRC），位于生物化学和结构生物学系 Joe R.和Teresa Lozano Long医学院。 XRC拥有20年的历史，是机构 研究核心研究副总裁副总裁和药物发现与结构的一部分 生物学在NCI指定的MAYS癌症中心共享资源。它提供结晶，x- 射线衍射数据收集和大分子结构确定服务 整个机构，其中心和圣安东尼奥地区的项目。仪器的用户是 癌症生物学，DNA损伤和维修，先天免疫，感染性等主题的研究者 疾病和药物设计仅举几例。 XRC中的当前资源包括一个Micromax 007HF X射线发电机，驱动两个端口 Varimax-HR和HF共聚焦光学元件针对两个固定的R轴HTC成像板检测器。 007HF 旋转阳极发生器已忠实地为XRC用户服务，并且将有效并支持多年 来到制造商Rigaku（自1951年以来从事商业）。但是，成像板检测器已经 由Rigaku逐步淘汰，不再有资格从今年开始获得零件支持。俩继续 增强XRC操作，我们建议用单个hypix-升级/替换两个检测器和光学。 6000他的光子计数检测器安装在通用的kappa goniemer和varimax vhf共聚焦上 微孔光学元件具有连续可调的发散缝隙组件。新仪器将是 安装在现有的X射线发生器上，取代两个过时的成像板系统，也将 使用现有的牛津冷冻流800冷却系统。成像板技术是两代 在技​​术的后面，由电荷耦合器件（CCD）检测器和现在的光子计数取代 探测器。 Hypix-6000HE明显优于成像板技术，并在CCD上有所改善 技术在该光子计数检测器具有高灵敏度和动态范围，同时消除了错误 由于读数噪声和深色电流。其他主要优势是数据的速度和量 可以通过我们的成像板上的光子计数检测器获取。 Hypix-6000他可以全面获得 图像板需要数小时到几天的时间范围内的数据集。总体而言， 要求升级到XRC将受益于快速，高质量，高分辨率数据收集的调查员 在短期内完成与人类健康相关的大分子的结构确定。