Biomolecular Structure Core

项目总结(生物分子结构核心) 对蛋白质、核酸及其复合体的三维结构的分析提供了独特的 对其生物学功能的洞察对于开发更好的预防或治疗疗法非常重要 人类疾病。生物分子结构核心(BSC)提供专业知识和最先进的仪器 用于结构确定和分析，以支持俄克拉荷马州科布雷下属的研究小组 结构生物学(OCSB)和其他参与俄克拉荷马州结构生物学研究的团体 在这一地区。BSC通过使用机器人仪器进行筛选来实现这一目的 结晶条件、高通量微聚焦X射线发生器和最先进的混合像素X射线探测器 用于快速数据收集以及处理和确定结构的计算资源 关注的大分子。布莱恩·穆尔斯博士(学术核心主任)和伦纳德·托马斯博士(设施 经理)都是全职博士结晶学家。核心雇用了一名工作人员科学家和一名研究生助理 帮助筛选结晶条件和制备用于收集X射线数据的样品。 CORE为对高分子感兴趣的学生、博士后研究员和教职员工提供培训 结构确定。平衡计分卡的服务涵盖结构确定的方方面面，包括 结晶筛选、晶体低温保护剂筛选、衍射数据采集与处理、结构 确定和细化、结构分析和解释、图形准备和结构沉积 在蛋白质数据库里。该核心还便于在国家同步加速器设施中收集衍射数据。 在第二阶段，在核心增加了一个分子建模单元，这一直在促进密集的 候选药物分子筛选、分子动力学模拟和分子的计算工作 替补。该装置还将用于小角X射线散射研究(SAXS)的分子模拟 数据和具有结构集合的低温电磁数据。 在OCSB筹资的第一和第二阶段，平衡计分卡的用户群从7个扩大到50多个用户组。至 在第三阶段推动用户基础的进一步扩大，BSC将扩大对解决方案的支持和推广- 基于结构确定方法，如SAXS和CRYO-EM。BSC学术核心总监 布莱恩·穆尔斯博士是SAXS专家，因此唯一有资格与研究人员在 需要这种方法论。在第二阶段，OCSB的资金被用于购买冷冻用的低温柱塞 用于冷冻EM的样品。此外，俄克拉荷马大学最近聘请了一名瞬变电磁专家作为工作人员科学家 其OU Samuel Roberts诺布尔显微镜实验室(SRNML)允许扩展到低温EM。这个 CORE正在与SRNML合作实施冷冻-EM技术，如冷冻网格准备和 初步收集数据，并为研究人员提供支持和培训，以便能够申请国家 低温电磁中心。平衡计分卡还将继续为结构确定提供仪器和服务 在第三阶段使用X射线结晶学。

Project Summary (Biomolecular Structure Core) The analysis of the three-dimensional structures of proteins, nucleic acids, and their complexes provides unique insights into their biological function that are important for developing better therapeutics to prevent or treat human diseases. The Biomolecular Structure Core (BSC) provides expertise and state-of-the-art instrumentation for structure determination and analysis to support research groups affiliated with the Oklahoma COBRE in Structural Biology (OCSB) and other groups involved in structural biology research across the State of Oklahoma and in the region. The BSC accomplishes this purpose by using robotic instrumentation for the screening of crystallization conditions, high-flux microfocus X-ray generators, and a state-of-the-art hybrid pixel X-ray detector for rapid data collection along with computational resources to process and determine the structure of the macromolecule of interest. Dr. Blaine Mooers (Academic Core Director) and Dr. Leonard Thomas (Facility Manager) are full-time Ph.D. crystallographers. The core employs a Staff Scientist and a Graduate Assistant to aid in the screening of crystallization conditions and the preparation of samples for the collection of X-ray data. The core provides training to students, postdoctoral fellows, and faculty who are interested in macromolecular structure determination. The services of the BSC encompass all aspects of structure determination including crystallization screening, crystal cryo-protectant screening, diffraction data collection and processing, structure determination and refinement, structure analysis and interpretation, figure preparation, and structure deposition in the Protein Data Bank. The core also facilitates diffraction data collection at national synchrotron facilities. During Phase 2, a Molecular Modeling Unit was added to the core, which has been facilitating intensive computational work for candidate drug molecule screening, molecular dynamics simulations, and molecular replacement. This unit will also be used for molecular modeling with small-angle X-ray scattering studies (SAXS) data and cryo-EM data with ensembles of structures. During Phases 1 and 2 of OCSB funding, the BSC’s user base expanded from 7 to over 50 user groups. To promote further expansion of the user base in Phase 3, the BSC will expand its support and promotion of solution- based structure determination methodologies, such as SAXS and cryo-EM. The BSC Academic Core Director Dr. Blaine Mooers is a SAXS expert and thus uniquely qualified to consult and collaborate with researchers in need of this methodology. During Phase 2, OCSB funding was used to purchase cryo-plungers for the freezing of samples for cryo-EM. In addition, the University of Oklahoma recently hired a TEM specialist as a staff scientist for its OU Samuel Roberts Noble Microscopy Laboratory (SRNML) to allow for the expansion into cryo-EM. The core is collaborating with the SRNML on implementing cryo-EM techniques such as cryo-grid preparation and initial data collection and providing support and training to researchers to be able to apply for time at national cryo-EM centers. The BSC will also continue to provide instrumentation and services for structure determination using X-ray crystallography during Phase 3.