Structural Dynamics at LCLS

LCLS 结构动力学

• 批准号: 10614410
• 负责人: Sebastien Boutet
• 金额: $ 3.67万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10614410
• 关键词: Active Sites; Adenine; Antibiotics; Area; Automobile Driving; Beds; Binding; Biochemical Reaction; Communities; Development; Emerging Technologies; Equilibrium; Goals; Life Cycle Stages; Light; Macromolecular Complexes; Membrane Proteins; Methodology; Methods; Molecular Conformation; Motivation; Neisseria gonorrhoeae; Process; RNA Polymerase II; Research; Research Personnel; Ribonucleotide Reductase; Roentgen Rays; Selection Criteria; Signal Transduction; Source; Specificity; Structure; Technology; Testing; Time; Training; United States National Institutes of Health; Variant; beta-Lactamase; cytochrome c oxidase; experimental study; improved; interest; macromolecule; metalloenzyme; method development; programs; technology development; temporal measurement; tool; willingness; x-ray free-electron laser

ABSTRACT: DRIVING BIOMEDICAL PROJECTS PORTFOLIO Nine Driving Biomedical Projects (DBP) are selected in this component of the proposed BTRR. These DBPs were selected based on high scientific merit as well as their need for X-ray methods to obtain structural and dynamic information that will reveal the detailed function of various biomolecules of interest. As such, they fulfil the primary purpose of providing scientific context and motivation for the technologies to be developed by the proposed BTRR. The DBPs will also provide necessary test beds for the developed technologies and create a virtuous cycle of iterative technology development that will lead to new broadly available capabilities for the biomedical community. The DBPs are organized along three themes. 1-Structure determination of large macromolecules and membrane proteins. 2-The determination of accurate active site structures of metalloenzymes, such as ribonucleotide reductase and cytochrome c oxidase, and complex macromolecular machines, such as RNA polymerase-II. 3-A common research area of all DBPs involve time-resolved (TR) studies that include research to follow dynamic processes involved in adenine riboswitch signaling, the transport mechanism of N. gonorrhoeae MtrF, antibiotic binding to β-lactamase and examination of interaction specificity of CypA variants. These DBPs will drive method developments in efficient structure determination using the Linac Coherent Light Source (LCLS). They will also drive the development of robust rapid mixing capabilities that will reveal antibiotic binding dynamics or enzymatic reactions with high spatial and temporal resolution, as well as new methods in light activated caged compound release and understanding conformational space dynamics in biomolecules using light to push them out of equilibrium. Overall, the proposed DBPs cover a breadth of scientific problems of high interest to the biomedical community and NIH and they represent a strong set of requirements that will push the BTRR technologies towards tools that will serve the biomedical community for the long term.

摘要：驾驶生物医学项目投资组合 在拟议的BTRR的这一组成部分中选择了九个驾驶生物医学项目（DBP）。 这些DBP是根据高科学优点以及对X射线方法的需求选择的 获得结构和动态信息，以揭示各种的详细功能 感兴趣的生物分子。因此，他们实现了提供科学环境的主要目的 和拟议BTRR开发的技术的动机。 DBP也将 为开发的技术提供必要的测试床，并创建一个虚拟的迭代周期 技术开发将为生物医学带来新的广泛可用功能 社区。 DBP沿三个主题组织。大型大分子的1个结构测定 和膜蛋白。 2-确定准确的活性位点结构 金属酶，例如核糖核苷酸还原酶和细胞色素C氧化酶，以及复合物 大分子机器，例如RNA聚合酶-II。 3-所有DBP的共同研究领域 涉及时间分辨（TR）研究，其中包括遵循涉及动态过程的研究 腺嘌呤核糖开关信号传导，淋病链球菌的传输机制，抗生素结合 到β-内酰胺酶和CYPA变体相互作用特异性的检查。 这些DBP将使用LINAC来驱动有效结构确定的方法开发 相干光源（LCLS）。他们还将推动强大的快速混合的发展 可以揭示抗生素结合动力学或酶促反应的能力 和临时分辨率以及光激活的笼中化合物释放中的新方法和 使用光线了解生物分子中的会议空间动态 平衡。 总体而言，拟议的DBP涵盖了广泛的科学问题，引起了人们的兴趣。 生物医学界和NIH，它们代表着一系列强大的要求，将推动 BTRR技术对将长期为生物医学界服务的工具。