Structural Dynamics at LCLS

LCLS 结构动力学

• 批准号: 10089011
• 负责人: Sebastien Boutet
• 金额: $ 44.25万
• 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/10089011
• 关键词: Algorithms; Area; Attention; Automation; Biochemical Reaction; Collaborations; Communities; Consumption; Crystallization; Data; Data Analyses; Data Collection; Data Set; Development; Development Plans; Equilibrium; Evolution; Failure; Feedback; G-Protein-Coupled Receptors; Goals; Human; Human Resources; Intervention; Lasers; Lighting; Measurement; Measures; Metalloproteins; Metals; Methods; Monitor; Optics; Outcome; Physiological; Process; Protein Dynamics; Proteins; Pump; RNA Polymerase II; Reaction; Resources; Safety; Sampling; Science; Series; Services; Signal Transduction; Source; Structure; System; Techniques; Temperature; Time; Ultraviolet Rays; Visible Radiation; base; beamline; biological systems; data analysis pipeline; data quality; data streams; experience; experimental study; improved; innovation; programs; sensor; software systems; structural biology; structural genomics; success; technology research and development; temperature jump; temporal measurement

ABSTRACT: TR&D-3 TR&D-3 will focus on automating the LCLS structural biology experiment, using injector-based sample delivery, streamlining the process of solving new structures, and examining dynamic processes of biomolecules using mixing injectors and photo-excitation to trigger reactions. Significant effort is required to fully automate the LCLS experiment that requires the addition of new controls and feedback sensors combined with adept implementation of advanced algorithms to monitor the experiment and make corrections or flag for intervention when appropriate. The extremely effective MC beam lines at SR sources show what decades of innovation in these areas can accomplish. The SSRL SMB program is experienced in experimental automation and were the first SR beamlines in the world to offer a remote-access program to SR users, establishing a new paradigm for SR access and structural genomic. TR&D-3 intends to duplicate the successes at SR sources in automation, and achieve similar accomplishments at LCLS, including automated sample delivery, data collection, data analysis and feedback for experiments at room temperature. Shorter times to collect datasets with real time feedback of data quality and completeness (and in the case of time resolved experiments, difference data metrics) will allow more structures to be determined, which in turn will allow users measuring a dynamic process, such as an enzymatic reaction, to get a more complete structural time series. More effective and, consequently, shorter data collection times will also allow more samples, users and access to the unique capabilities of LCLS leading to a broader scientific impact in biomedical applications. With the study of dynamics under near physiological conditions being at the core of LCLS applications, this TR&D will provide enhanced visible light excitation capabilities and injector alignment to support time resolved studies, including the use of mixing injectors and laser illumination to trigger reactions. The use of laser-released caged compounds will drive dynamics studies of GPCRs and RNA polymerase-II. Laser-induced temperature jump capabilities will drive the goal of understanding protein dynamics by exciting them out of equilibrium and tracking the time-evolution of the system. Overall, TR&D-3 will aim to achieve the scientific goals of all the DBPs through improved reliability and automation of the entire experimental process.

摘要：TR&D-3 TR&D-3将专注于自动化LCLS结构生物学实验，使用基于注射器的 样品交付，简化解决新结构的过程，并检查动态 使用混合注射器和光激发来触发反应的生物分子的过程。 需要大量的工作来完全自动化LCLS实验，该实验需要添加 新的控制和反馈传感器与先进算法的巧妙实施相结合 监测实验，并在适当时进行纠正或标记干预。的 SR源上极其有效的MC束线显示了这些领域数十年来的创新 可以完成。SSRL SMB计划在实验自动化方面经验丰富， 世界上第一个为SR用户提供远程访问程序的SR波束线，建立了一个 SR访问和结构基因组学的新范例。TR&D-3打算复制成功 在自动化SR源，并在LCLS实现类似的成就，包括自动化 样品输送、数据收集、数据分析和反馈，用于室温下的实验。 缩短收集数据集的时间，并对数据质量和完整性进行真实的反馈（以及 在时间分辨实验的情况下，差异数据度量）将允许更多的结构被 确定，这反过来将允许用户测量动态过程，如酶促反应， 反应，以获得更完整的结构时间序列。更有效，因此更短 数据收集时间也将允许更多的样本，用户和访问的独特能力， LCLS在生物医学应用中产生更广泛的科学影响。 近生理条件下的动力学研究是LCLS的核心 应用，该TR&D将提供增强的可见光激发能力和注入器 校准以支持时间分辨研究，包括使用混合注射器和激光 照明以引发反应。使用激光释放的笼状化合物将推动动力学 GPCR和RNA聚合酶-II的研究。激光诱导的温度跳跃能力将推动 我们的目标是通过激发蛋白质的平衡状态来了解蛋白质动力学， 系统的时间演化。总的来说，TR&D-3将致力于实现所有科学目标。 DBPs通过提高整个实验过程的可靠性和自动化。