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：驱动生物医学项目组合