Development of Serial Micro-crystallography

系列微晶体学的发展

• 批准号: 10093086
• 负责人: Robert William Henning
• 金额: $ 30.95万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10093086
• 关键词: Address; Area; Automobile Driving; Biochemical Reaction; Biological; Biological Process; Catalysis; Characteristics; Charge; Chemicals; Collimator; Communities; Complex; Computer software; Consumption; Coupled; Crystallization; Crystallography; Data; Data Collection; Development; Devices; Diffusion; Disease; Engineering; Enzymes; Freezing; Goals; Image; In Situ; Infrastructure; Integral Membrane Protein; Knowledge; Lasers; Light; Lighting; Measurement; Medical; Methods; Microfluidic Microchips; Microfluidics; Molecular; Molecular Conformation; Motion; Optics; Pattern; Pharmacology; Physiologic pulse; Physiological; Process; Proteins; Radiation induced damage; Reaction; Regulation; Resolution; Roentgen Rays; Rotation; Sampling; Scanning; Science; Services; Signal Transduction; Source; Spectrophotometry; Spectrum Analysis; Speed; Structure; Sulfamethoxazole; Synchrotrons; System; Technology; Temperature; Therapeutic; Time; Training; Viscosity; Work; X ray diffraction analysis; X-Ray Crystallography; base; beamline; biological research; chemical reaction; cofactor; computerized data processing; crystallinity; design; detector; electric field; experimental study; flexibility; improved; instrumentation; macromolecule; new technology; novel; novel strategies; open source; practical application; programs; protein function; rapid technique; software development; technology research and development; time use; tool development; transmission process; user-friendly

Abstract A major goal is biomedical science is to move beyond static images of proteins and other biological macromolecules to the internal dynamics underlying their function. This level of study is necessary to understand how these molecules work, to engineer new functions, and to rationally develop therapeutics. In this application, we propose two technological research and development projects that take advantage of the special characteristics of the BioCARS national synchrotron facility to address these goals. In the first, TR&D 1, we describe time-resolved serial micro-crystallography (TR-SMX) coupled with initiation of chemical reactions within molecules. This approach is enabled by the high intensity and tight focusing of X-rays at BioCARS, the availability of a large area, fast detectors, and the use of novel crystal injectors and microfluidic mixers. TR- SMX enables users to observe the dynamics of molecules as they execute their biological function at physiological temperatures. In the second, TR&D 2, we describe electric field-stimulated X-ray crystallography (EFX), a new method visualizing conformational changes within proteins and other biological macromolecules. This method uses external electric fields to induce global, subtle motions of atoms within proteins, with readout using time-resolved X-ray diffraction. Initial work demonstrates the practical application of EFX, and confirms the ability to globally excite motions throughout a protein molecule, including those of biological relevance. Since charges and dipoles are universally present in macromolecules, EFX represents, in principle, a general approach for intramolecular dynamics. We describe several user-based driving biomedical projects and collaborative and service projects that cover a wide range of important problems and push both technologies. User training and active approaches to dissemination to both expert and non-expert, wider audiences will enable broad use of the new technologies by the scientific community.

摘要