The Crystallography of Macromolecules

高分子晶体学

• 批准号: 7260037
• 负责人: ZBYSZEK OTWINOWSKI
• 金额: $ 46.33万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7260037
• 关键词: Address; Algorithms; Area; Back; Basic Science; Collection; Communication; Communities; Complex; Condition; Crystallization; Crystallography; Data; Data Analyses; Data Collection; Data Quality; Data Set; Data Storage and Retrieval; Databases; Development; Diagnostic; Dose; Drug Design; Effectiveness; Excision; Expert Systems; Goals; Grant; Ice; Mainstreaming; Measurement; Measures; Methods; Modeling; Monitor; Morphologic artifacts; Nucleic Acids; Numbers; Numeric Rating Scale; Pattern; Phase; Production; Protocols documentation; Radiation induced damage; Research Personnel; Resolution; Resources; Schedule; Shapes; Signal Transduction; Specific qualifier value; Speed; Statistically Significant; Structure; System; Techniques; Technology; Twin Multiple Birth; Work; base; data acquisition; data management; design; desire; detector; frontier; improved; independent component analysis; macromolecule; method development; novel; novel strategies; parallel computing; parallel processing; programs; protein structure; research study; scale up; small molecule; statistics; tool

DESCRIPTION (provided by applicant): The great demand from basic science and drug design for detailed, atomic level information about the structure of proteins and nucleic acids resulted in a large-scale experimental effort, with crystallography being its predominant technique. The aim of this grant is to improve methods of crystallographic diffraction data analysis in the areas of data collection, integration of diffraction peaks, scaling and merging. The methods address both the mainstream use and the frontiers of crystallography. Improvements to the core of current methods will result from the precise modeling of diffraction peaks' shape, the removal of diffraction artifacts, the corrections for radiation damage-induced effects and the better diagnostics of possible problems, like pseudo symmetry and/or twinning etc. The challenging structural projects require complex optimization of crystallization and cryo-protection conditions. Such projects benefit greatly from averaging, if possible, the data from multiple crystals, so far mostly avoided due to lack of appropriate tools. We plan to develop a novel type of diffraction signal analysis that will compare data from multiple crystals to define their diffraction quality and consistency. Data from multiple crystals will be decomposed into statistically significant signals, including the desired phasing signals and the description of non-isomorphism. The results of this analysis will be straightforward to interpret and optimal in terms of averaging data from not necessarily exactly isomorphous crystals. This development is particularly significant due to the technology scaling up the production of crystals and the collection of diffraction data. The improved effectiveness of the experimental work will result also from the expanded experiment planning tools, automatic interactions with external databases, data management tools and parallel computing. The developed algorithms and methods will be implemented in the HKL2000 suite, widely used by the crystallographic community.

描述（由申请人提供）：基础科学和药物设计对有关蛋白质和核酸结构的详细原子级信息的巨大需求导致了大规模的实验工作，其中晶体学是其主要技术。这笔赠款的目的是改进数据收集、衍射峰积分、缩放和合并领域的晶体衍射数据分析方法。这些方法既涉及主流用途，又涉及晶体学的前沿。对当前方法核心的改进将来自于衍射峰形状的精确建模、衍射伪影的消除、辐射损伤引起的效应的校正以及对可能问题（如伪对称和/或孪生等）的更好诊断。具有挑战性的结构项目需要对结晶和低温保护条件进行复杂的优化。如果可能的话，这些项目可以从多个晶体的数据平均中受益匪浅，但到目前为止，由于缺乏适当的工具，大多数情况下都避免了这种情况。我们计划开发一种新型的衍射信号分析，该分析将比较多个晶体的数据，以确定它们的衍射质量和一致性。来自多个晶体的数据将被分解为具有统计意义的信号，包括所需的定相信号和非同构的描述。该分析的结果将很容易解释，并且根据不一定完全同质晶体的平均数据进行优化。由于扩大了晶体生产规模和衍射数据收集的技术，这一发展尤为重要。实验工作效率的提高还得益于实验计划工具的扩展、与外部数据库的自动交互、数据管理工具和并行计算。开发的算法和方法将在晶体学界广泛使用的 HKL2000 套件中实施。