Dynamical Diffraction Analysis for 3D Electron Crystallography

3D 电子晶体学的动态衍射分析

• 批准号: 10546970
• 负责人: Raquel Bromberg
• 金额: $ 25万
• 依托单位: LIGO ANALYTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2023-11-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10546970
• 关键词: 3-Dimensional; Academia; Address; Agreement; Area; Automobile Driving; Characteristics; Chemical Structure; Chemicals; Complex; Computer software; Contracts; Crystallization; Crystallography; Custom; Data; Data Analyses; Data Collection; Data Set; Drug Approval; Electron Microscopy; Electrons; Handedness; Image; Industrialization; Industry; Laboratory Research; Legal; Methods; Modeling; Modulus; Motion; Phase; Powder dose form; Process; Radiation; Regulation; Resolution; Rotation; Sampling; Science; Series; Signal Transduction; Small Business Innovation Research Grant; Spottings; Structure; Testing; Three-dimensional analysis; Toxic effect; Trust; Work; X ray diffraction analysis; X-Ray Crystallography; base; commercialization; data acquisition; data quality; electron crystallography; electron diffraction; experience; improved; indexing; interest; multiple datasets; nanocrystal; novel; novel strategies; small molecule; submicron

Project Abstract Diffraction methods generate detailed structural information for chemical compounds, driving discoveries in many fields across academia and industry. The standard approaches use either single crystals, which provide highly informative data, or powders of nanocrystals, which provide less information. Microcrystal electron diffraction (microED) has all the data richness benefits of single crystal crystallography and works with small crystals. However, the methods for microED data acquisition and analysis are not yet mature enough to provide results with quality and reliability comparable to X-ray crystallography. The challenges include absolute configuration determination, efficient data collection, and diffraction data analysis in the presence of microED-specific experimental errors. In SBIR Phase I, we will develop, implement, and test methods that address handedness determination for small molecule crystals and combine them with effective approaches to greatly reduce systematic errors, to enable merging datasets from multiple crystals, experimental phasing and absolute configuration determination. In SBIR Phase II, we will expand and incorporate these solutions into an easy-to- use, complete crystallographic package for microED and also validate the approach in a broad range of experimental conditions, tailoring the solutions to characteristic problems. These new methods will benefit all types of microED analysis and result (1) in absolute configuration determination for all type of compounds, (2) expanded applicability to radiation-sensitive and other difficult-to- handle crystals, and (3) better agreement between the model and the data which will increase the trust in results, in particular for de novo structure determination. These benefits are of high significance for this quickly expanding field, so the potential for successful commercialization is high.

项目摘要 衍射法为化合物生成详细的结构信息，推动了许多 学术界和工业界的各个领域。标准的方法使用单晶体，它提供了高度的 信息性数据，或纳米晶体粉末，提供的信息较少。微晶电子衍射 (MicroED)具有单晶结晶学的所有数据丰富性优势，并且适用于小晶体。 然而，获取和分析microED数据的方法还不够成熟，不能提供结果 质量和可靠性可与X射线结晶学相媲美。挑战包括绝对配置 在存在微ED特异性的情况下的测定、有效的数据收集和衍射数据分析 实验错误。在SBIR第一阶段，我们将开发、实现和测试解决惯用手问题的方法 对小分子晶体的测定，并结合有效的方法大大减少 系统误差，以支持合并来自多个晶体的数据集、实验相位和绝对 配置确定。在SBIR第二阶段，我们将扩展这些解决方案并将其整合到一个易于 使用完整的微电子衍射晶体包，并在广泛的范围内验证方法 实验条件，针对特征问题量身定做解决方案。 这些新方法将有利于所有类型的微电子能谱分析和结果(1)的绝对构型 对所有类型化合物的测定，(2)扩大了对辐射敏感和其他难以测定的化合物的适用性。 处理晶体，以及(3)模型和数据之间更好的一致性，这将增加对结果的信任， 特别是用于从头结构测定。这些好处对于这种快速扩张具有非常重要的意义 因此，成功商业化的潜力很大。