High throughput laboratory X-ray illumination system for protein crystallography and screening

用于蛋白质晶体学和筛选的高通量实验室 X 射线照明系统

• 批准号: 9336950
• 负责人: Wenbing Yun
• 金额: $ 67.14万
• 依托单位: SIGRAY, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-18 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9336950
• 关键词: Active Sites; Agriculture; Alpha Cell; Alzheimer' s Disease; Anodes; Antibodies; Area; Biological Process; Biological Sciences; Bioremediations; Budgets; Characteristics; Chemicals; Clinical; Collaborations; Computer Simulation; Coupled; Crystallization; Crystallography; DNA; Dangerousness; Databases; Deposition; Development; Diabetes Mellitus; Diamond; Drug Design; Elements; Environment; Enzymes; Excision; Food; Genetic Materials; HGF gene; High temperature of physical object; Industrialization; Knowledge; Laboratories; Legal patent; Letters; Lighting; Liquid substance; Macular degeneration; Malignant Neoplasms; Metabolic Pathway; Metals; Methods; Molecular Structure; Neurodegenerative Disorders; New York; Nucleic Acids; Optics; Pattern; Performance; Pharmaceutical Preparations; Pharmacology; Phase; Play; Principal Investigator; Process; Production; Property; Protein Engineering; Proteins; RNA; Regulatory Pathway; Research; Roentgen Rays; Role; Signal Transduction; Source; Speed; Structure; Synchrotrons; System; Techniques; Testing; Therapeutic; Therapeutic Clinical Trial; Thermal Conductivity; Training; Universities; Viral Proteins; Virus; X-Ray Crystallography; base; beamline; density; design; drug development; drug discovery; engineering design; experimental study; high throughput screening; human disease; improved; innovation; insight; interest; macromolecule; novel; operation; programs; protein structure; prototype; screening; structural biology; therapeutic target; three dimensional structure; tool; virus genetics; wasting

Title: High performance, high throughput laboratory x-ray illumination system for protein crystallography Project Summary and Abstract X-ray protein crystallography is the leading method for determining the 3D structures of macromolecules (proteins, viruses, nucleic acids). Structural understanding provides key insight into their functionality and is now an essential tool for industrial applications in food & agriculture, protein engineering, and drug design. This has resulted in several high profile late-stage clinical drug trials for cancer and Alzheimer’s therapeutics. We propose to develop an X-ray illumination system comprising a proprietary x-ray source and x-ray optic optimized for the Single-Wavelength Anomalous Dispersion (SAD) approach to x-ray crystallography. This illumination beam system is designed to deliver x-ray energies that optimize the signal of commonly used scatterers in the SAD technique, and will furthermore provide 8X higher flux than current state-of-the-art laboratory x-ray sources. The key innovations include a novel pattern and new materials for the x-ray source targets and an axially symmetric x-ray optical train that provides a small crossfire for the illumination beam. This proposed phase II project will result in the development of a prototype of the illumination beam system and experimental demonstration of the intended specifications and parameters.

标题：用于蛋白质晶体学的高性能、高通量实验室X射线照明系统 项目概要和摘要 X射线蛋白质晶体学是确定大分子3D结构的主要方法 （蛋白质、病毒、核酸）。结构理解提供了对其功能的关键洞察， 现在是食品和农业、蛋白质工程和药物设计等工业应用的重要工具。 这导致了几个备受瞩目的癌症和阿尔茨海默氏症治疗的后期临床药物试验。 我们建议开发一种X射线照明系统，包括专有的X射线源和X射线光学器件 针对X射线晶体学的单波长异常色散（SAD）方法进行了优化。这 照明光束系统被设计成传递X射线能量 在SAD技术中的散射体，并且将进一步提供比当前最先进的技术高8倍的通量 实验室X射线源关键的创新包括X射线源的新图案和新材料 目标和轴对称的X射线光学系统，其为照明光束提供小的交叉照射。 这个拟议的第二阶段项目将导致开发照明光束系统的原型 以及预期规格和参数的实验验证。