Biomolecular Structure Core

生物分子结构核心

• 批准号: 10631172
• 负责人: Leonard M Thomas
• 金额: $ 28.54万
• 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/10631172
• 关键词: Award; Biological Process; Centers of Research Excellence; Collaborations; 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; Group Affiliation; Growth; Health; Health Sciences; Human; Hybrids; Institution; Knowledge; Laboratories; Literature; Methodology; Methods; Microscopy; Molecular; Molecular Structure; Nucleic Acids; Oklahoma; Outcome; Output; Peer Review; Phase; Play; Postdoctoral Fellow; Preparation; Process; Proteins; Publications; Qualifying; 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） 蛋白质、核酸及其复合物的三维结构分析提供了独特的 深入了解它们的生物学功能，对于开发更好的治疗方法来预防或治疗 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 用于结构测定和分析，以支持隶属于俄克拉荷马州COBRE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 在该地区。BSC通过使用机器人仪器来筛选 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 用于快速数据收集沿着计算资源以处理和确定 感兴趣的大分子。Blaine Mooers博士（学术核心主任）和伦纳德托马斯博士（机构 博士（Ph.D.）结晶学家核心雇用了一名科学家和一名研究生助理， 有助于筛选结晶条件和制备用于收集X射线数据的样品。 该中心为对大分子生物学感兴趣的学生、博士后研究员和教师提供培训 结构测定BSC的服务包括结构确定的所有方面， 结晶筛选，晶体防冻剂筛选，衍射数据采集与处理，结构 确定和细化、结构分析和解释、图形制备和结构沉积 在蛋白质数据库中。该核心还促进了国家同步加速器设施的衍射数据收集。 在第二阶段，核心增加了一个分子建模单元， 用于候选药物分子筛选、分子动力学模拟和分子生物学的计算工作。 更换.该单元也将用于小角X射线散射研究（SAXS）的分子建模 数据和具有结构集合的低温EM数据。 在OCSB资助的第一阶段和第二阶段，BSC的用户群从7个扩展到50多个用户群。到 在第三阶段，BSC将进一步扩大其对解决方案的支持和推广， 基于结构测定方法，如SAXS和cryo-EM。BSC学术核心主任 博士Blaine Mooers是一位SAXS专家，因此具有独特的资格与研究人员进行咨询和合作， 需要这种方法。在第二阶段，OCSB的资金用于购买冷冻柱塞， 冷冻电镜的样本此外，俄克拉荷马州大学最近聘请了一位TEM专家作为科学家 Samuel Roberts Noble显微镜实验室（SRNML），允许扩展到冷冻EM。的 核心正在与SRNML合作实施低温EM技术，如低温网格制备， 初步数据收集，并向研究人员提供支持和培训，使他们能够申请国家研究所的时间， 冷冻电镜中心BSC还将继续为结构确定提供仪器和服务 在第三阶段使用X射线晶体学。