Structural Dynamics at LCLS

摘要：R&D-1 要使超额订阅的LCLS源上的波束时间用于科学发现，而不是 实验优化，此研发项目下的活动旨在开发工具 必须为生物医学实验做充分准备，并在此之前对样品进行表征 并且在LCLS波束时间期间。这包括了解样品的质量和特性， 以及在复杂样品输送期间或在动态过程期间样品的状态 正在研究中。通过这项研发，SLAC的现有能力将得到增强，提供新的 样品制备和表征方面的工具，以及了解 样本的状态。此外，SSRL的功能将得到利用和扩展以使用 作为LCLS光束时间和新科学准备的关键工具的同步加速器X射线束。 最后，LCLS的样品表征的光谱能力将得到扩展。 拟议的研发范围是生物医学结构生物学领域的前沿，通过 利用X射线自由电子激光能力解算新结构和研究分子动力学 在接近生理条件下的环境温度下。拟议的发展项目将 利用最先进的X射线FEL功能并与离线功能相辅相成 它们本身就代表着尖端的进步。研发将增加总和 通过为LCLS提供更高的就绪性级别，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。通过提高效率，“额外的”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。通过对X射线自由电子激光样品的制备 以及从艺术到定量科学的交付，预计LCLS和这一BTRR将 对络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中心结构，并提供增强和更多 使用组合功率观察大分子动力学的广泛可用的能力 LCLS和SSRL。

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.