Biomolecular Structure Core

生物分子结构核心

• 批准号: 10413482
• 负责人: Leonard M Thomas
• 金额: $ 28.88万
• 依托单位: UNIVERSITY OF OKLAHOMA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10413482
• 关键词: Award; Biological Process; Centers of Research Excellence; Collection; Communities; Competence; Complex; Consult; Cryoelectron Microscopy; Crystallization; Crystallography; Data; Data Collection; Deposition; Development; Doctor of Philosophy; Education and Outreach; Educational workshop; Ensure; Equipment; Faculty; Fees; Freezing; Funding; Geography; Grant; Growth; Health; Health Sciences; Human; Hybrids; Knowledge; Laboratories; Literature; Methodology; Methods; Microscopy; Molecular; Molecular Structure; Nucleic Acids; Oklahoma; Outcome; Output; Peer Review; Phase; Play; Postdoctoral Fellow; Preparation; Process; Proteins; Publications; Reporting; Research; Research Personnel; Research Project Grants; Research Support; Resolution; Resources; Robotics; Roentgen Rays; Role; Sampling; Scientist; Services; Specialist; Structural Biologist; Structure; Students; Synchrotrons; Techniques; Therapeutic; Three-dimensional analysis; Time; Training; Universities; Work; X-Ray Crystallography; base; computer infrastructure; computerized data processing; computing resources; design; detector; drug candidate; graduate student; human disease; improved; insight; instrument; instrumentation; interest; literacy; macromolecule; molecular dynamics; molecular modeling; next generation; novel therapeutics; prevent; programs; protein data bank; sample collection; screening; structural biology; three dimensional structure; undergraduate student

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.

项目概要（生物分子结构核心） 对蛋白质、核酸及其复合物的三维结构的分析提供了独特的 深入了解其生物学功能对于开发更好的预防或治疗疗法非常重要 生物分子结构核心 (BSC) 提供专业知识和最先进的仪器。 用于结构测定和分析，以支持俄克拉荷马州 COBRE 附属研究小组 结构生物学 (OCSB) 和俄克拉荷马州参与结构生物学研究的其他团体 在该地区，平衡计分卡通过使用机器人仪器进行筛查来实现这一目的。 结晶条件、高通量微焦点 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计算资源来处理和确定结构 感兴趣的大分子。 Blaine Mooers 博士（学术核心主任）和 Leonard Thomas 博士（设施） 经理）是全职晶体学家，核心聘有一名研究员和一名研究生助理。 帮助筛选结晶条件和制备用于收集 X 射线数据的样品。 该核心为对高分子感兴趣的学生、博士后和教师提供培训 结构确定。平衡计分卡的服务涵盖结构确定的所有方面，包括 结晶筛选、晶体冷冻保护剂筛选、衍射数据收集和处理、结构 确定和细化、结构分析和解释、图形准备和结构沉积 该核心还有助于国家同步加速器设施的衍射数据收集。 在第二阶段，在核心中添加了分子建模单元，这促进了密集型 候选药物分子筛选、分子动力学模拟和分子生物学的计算工作 该装置还将用于小角度 X 射线散射研究 (SAXS) 的分子建模。 数据和带有结构集合的冷冻电镜数据。 在 OCSB 资助的第一阶段和第二阶段，BSC 的用户群从 7 个扩大到 50 多个用户组。 为推动第三阶段用户群的进一步扩大，BSC将扩大对解决方案的支持和推广—— 基于结构测定的方法，例如 SAXS 和冷冻电镜 BSC 学术核心主任。 Blaine Mooers 博士是 SAXS 专家，因此具有与以下领域的研究人员进行咨询和合作的独特资格： 在第二阶段，OCSB 资金用于购买冷冻柱塞。 此外，俄克拉荷马大学最近聘请了一名 TEM 专家作为科学家。 其 OU Samuel Roberts Noble 显微镜实验室 (SRNML) 能够扩展到冷冻电镜领域。 core 正在与 SRNML 合作实施冷冻电镜技术，例如冷冻网格准备和 初步数据收集并向研究人员提供支持和培训，以便能够申请国家研究的时间 BSC 还将继续为结构测定提供仪器和服务。 在第 3 阶段使用 X 射线晶体学。