Structural Dynamics at LCLS

LCLS 结构动力学

• 批准号: 10379225
• 负责人: Mark Hunter
• 金额: $ 50.66万
• 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/10379225
• 关键词: Active Sites; Arts; Automobile Driving; Biomedical Research; Collaborations; Communities; Complement; Complex; Data; Databases; Development; Development Plans; Dose; 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 在超认购的LCLS源中启用Beamtime用于科学发现，而不是 实验优化，此TR＆D下的活动旨在开发工具 为了充分准备生物医学实验并表征样品之前所必需的 在LCLS束时。从了解样本质量和特性， 以及在复杂样品传递期间或在动态过程中样本状态 正在研究。 SLAC的现有功能将通过此TR＆D增强，提供新的功能 样本准备和表征以及新诊断的工具，以了解 样本状态。此外，SSRL的功能将被利用并增加用于使用 Synchrotron X射线光束是为LCLS Beam Time和新科学准备的关键工具。 最后，将扩展用于LCLS样品表征的光谱功能。 提出的TR＆D范围位于生物医学结构生物学领域的前沿 利用X射线F​​EL功能来解决新结构并研究分子的动力学 在环境温度下的近乎生理条件下。拟议的发展将 利用最先进的X射线FEL功能，并通过离线功能完成它们 本身代表了前沿的进步。 TR＆D将增加组合 通过为LCL提供更高的准备水平，技术对生物医学研究的影响 在较短时间内进行更高质量数据的实验。通过提高效率，“额外”光束 时间访问将用于额外的高风险更高奖励实验。它也将允许 更快地解决了新兴的科学问题。通过服用X射线F​​EL样品制备 从艺术到定量科学，可以预期LCLS和BTRR将会 对复合物和膜蛋白的结构确定有重大影响， 提供金属酶的精确活性位点结构，并提供增强和更多 使用联合力量观察大分子动力学的广泛可用功能 LCLS和SSRL。