Structural Dynamics at LCLS

LCLS 结构动力学

• 批准号: 10614405
• 负责人: Mark Hunter
• 金额: $ 36.24万
• 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/10614405
• 关键词: Active Sites; Automobile Driving; Biomedical Research; Collaborations; Communities; Complement; Complex; Data; Databases; Development; Development Plans; Dose; Electronics; Ensure; Goals; In Situ; Laboratories; Measurement; Membrane Proteins; Methods; Monitor; Performance; Physiological; Preparation; Process; Property; Readiness; Research; Roentgen Rays; Sampling; Science; Services; Site; Source; Structure; Synchrotrons; Technology; Temperature; Time; Work; X ray diffraction analysis; experimental study; high reward; high risk; improved; interest; laboratory equipment; metalloenzyme; novel diagnostics; structural biology; success; technology development; technology research and development; tool; wasting; x-ray free-electron laser

ABSTRACT: TR&D-1 To enable beamtime at the oversubscribed LCLS source to be used for scientific discovery, not experiment optimization, the activities under this TR&D are aimed at developing the tools necessary to fully prepare for biomedical experiments and to characterize samples both before and during LCLS beam time. This ranges from understanding the sample quality and properties, as well as the state of the sample during complex sample delivery, or during a dynamic process being studied. The existing capabilities of SLAC will be enhanced via this TR&D, providing new tools in sample preparation and characterization, as well as new diagnostics to understand the state of the sample. Furthermore, capabilities at SSRL will be leveraged and augmented to use the synchrotron X-ray beam as a key tool to prepare for LCLS beamtime and for new science. Finally, spectroscopic capabilities for sample characterization at LCLS will be expanded. The proposed TR&D scope is at the cutting-edge of the biomedical structural biology field by exploiting X-ray FEL capabilities to solve new structures and study the dynamics of molecules under near-physiological conditions at ambient temperatures. The proposed developments will make use of state-of-the-art X-ray FEL capabilities and complement them with offline capabilities that themselves represent cutting-edge advances. The TR&D will increase the combined technologies’ impact on biomedical research by providing higher readiness levels to LCLS experiments for higher quality data in a shorter time. By increasing efficiency, the “extra” beam time access will be used for additional higher-risk, higher-reward experiments. It will also allow more rapid access to solve emerging scientific questions. By taking X-ray FEL sample preparation and delivery from an art to a quantitative science, it is expected that LCLS and this BTRR will have a significant impact in the structure determination of complexes and membrane proteins, provide accurate active site structures of metalloenzymes, and provide enhanced and more broadly available capabilities to observe macromolecular dynamics using the combined powers of LCLS and SSRL.

摘要：TR&D-1 为了使超额订阅的 LCLS 源的波束时间能够用于科学发现，而不是 实验优化，该 TR&D 下的活动旨在开发工具 为生物医学实验做好充分准备并在之前对样品进行表征是必要的 以及 LCLS 光束时间期间。这包括了解样品的质量和特性， 以及复杂样品输送或动态过程中样品的状态 正在研究中。 SLAC 的现有能力将通过此次 TR&D 得到增强，提供新的 样品制备和表征的工具，以及新的诊断方法来了解 样品的状态。此外，SSRL 的能力将得到利用和增强，以使用 同步加速器 X 射线束作为准备 LCLS 射束时间和新科学的关键工具。 最后，LCLS 样品表征的光谱能力将得到扩展。 拟议的 TR&D 范围处于生物医学结构生物学领域的前沿 利用 X 射线 FEL 功能求解新结构并研究分子动力学 在环境温度的接近生理条件下。拟议的发展将 利用最先进的 X 射线 FEL 功能并通过离线功能对其进行补充 它们本身就代表了尖端的进步。 TR&D 将增加综合 通过为 LCLS 提供更高的准备水平，技术对生物医学研究的影响 在更短的时间内获得更高质量的数据的实验。通过提高效率，“额外”光束 时间访问将用于额外的高风险、高回报的实验。它还将允许 更快速地解决新出现的科学问题。通过采取X射线FEL样品制备 以及从艺术到定量科学的交付，预计 LCLS 和 BTRR 将 对复合物和膜蛋白的结构测定有重大影响， 提供准确的金属酶活性位点结构，并提供增强和更多 使用组合能力观察大分子动力学的广泛可用功能 LCLS 和 SSRL。