Structural Dynamics at LCLS

摘要：TR&D-1 为了使超额订购的LCLS源处的波束时间能够用于科学发现， 实验优化，本TR&D下的活动旨在开发工具 为了充分准备生物医学实验和表征样品， 以及在LCLS射束时间期间。这包括了解样品的质量和性质， 以及在复杂样品输送期间或在动态过程期间样品的状态 被研究。SLAC的现有能力将通过本TR&D得到增强， 样品制备和表征工具，以及新的诊断方法，以了解 样品的状态。此外，将利用和增强SSRL的能力， 同步加速器X射线束是为LCLS束流时间和新科学做准备的关键工具。 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射线自由电子激光的能力来解决新的结构和研究分子的动力学 在接近生理的环境温度下。拟议的发展将 利用最先进的X射线自由电子激光（FEL）功能，并以离线功能对其进行补充 它们本身就代表着最前沿的技术。TR&D将增加 技术对生物医学研究的影响，为LCLS提供更高的准备水平 在更短的时间内获得更高质量的数据。通过提高效率， 时间访问将用于额外的高风险，高回报的实验。它还将允许 更快地解决新出现的科学问题。通过X射线自由电子激光样品制备 从艺术到定量科学的交付，预计LCLS和BTRR将 在复合物和膜蛋白的结构测定中具有显著影响， 提供准确的金属酶活性位点结构，并提供增强的和更多的 广泛使用的能力，以观察大分子动力学使用的组合功率 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.