Structural Dynamics at LCLS

LCLS 结构动力学

• 批准号: 10614407
• 负责人: Sebastien Boutet
• 金额: $ 42.2万
• 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/10614407
• 关键词: Algorithms; Area; Attention; Automation; Biochemical Reaction; Collaborations; Communities; Consumption; Data; Data Analyses; Data Collection; Data Set; Development; Development Plans; Electronics; Equilibrium; Evolution; Failure; Feedback; G-Protein-Coupled Receptors; Genomics; 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; beamline; biological systems; data analysis pipeline; data quality; data streams; experience; experimental study; improved; innovation; programs; sensor; software systems; structural biology; 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将使用基于喷油器的LCLS结构生物学实验自动化自动化 样品输送，简化解决新结构的过程并检查动态 生物分子的过程使用混合注射器和光启示以触发反应。 需要大量的努力才能完全自动化LCLS实验，该实验需要添加 新的控件和反馈传感器结合了高级算法的熟练实现 监视实验并在适当时进行校正或标记以进行干预。这 SR来源极有效的MC线线显示了这些地区几十年的创新 可以完成。 SSRL SMB计划在实验自动化方面经历了 世界上第一个为SR用户提供远程访问程序的SR光束线，建立一个 用于SR访问和结构基因组的新范式。 TR＆D-3打算复制成功 在自动化中的SR来源，并在LCL中取得类似的成就，包括自动化 样品输送，数据收集，数据分析和在室温下实验的反馈。 较短的时间收集具有数据质量和完整性的实时反馈的数据集（以及 在时间解决实验的情况下，差异数据指标）将允许更多的结构为 确定，这反过来将允许用户测量动态过程，例如酶促 反应，获得更完整的结构时间序列。更有效，因此更短 数据收集时间还将允许更多样本，用户并访问唯一功能 LCLS导致对生物医学应用产生更广泛的科学影响。 在近乎生理条件下的动力学研究是LCL的核心 应用程序，此TR＆D将提供增强的可见光激发功能和喷油器 支持时间解决研究的对准，包括使用混合注射器和激光 照明以触发反应。使用激光释放的笼子化合物将驱动动态 GPCR和RNA聚合酶-II的研究。激光引起的温度跳跃能力将驱动 通过使蛋白质动态刺激蛋白质动态的目的 系统的时间进化。总体而言，TR＆D-3将旨在实现所有的科学目标 DBP通过提高可靠性和整个实验过程的自动化。