The Crystallography of Macromolecules

描述(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水平信息的巨大需求导致了大规模的实验工作，结晶学是其主要技术。这笔赠款的目的是在数据收集、衍射峰积分、定标和合并方面改进晶体衍射数据分析的方法。这些方法既涉及结晶学的主流用途，也涉及结晶学的前沿。当前方法的核心将通过对衍射峰形状的精确建模、衍射伪影的去除、辐射损伤效应的校正以及对可能出现的问题(如伪对称和/或孪晶等)的更好诊断而产生。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，这些项目从平均来自多个晶体的数据中受益匪浅，到目前为止，由于缺乏适当的工具，这些数据大多被避免了。我们计划开发一种新型的衍射信号分析，它将比较来自多个晶体的数据，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成统计上有意义的信号，包括所需的相位信号和非同构的描述。这种分析的结果将是直接解释的，并且在平均不一定是完全同构的晶体的数据方面是最优的。这一发展尤其重要，因为这项技术扩大了晶体的生产并收集了衍射数据。扩大的实验规划工具、与外部数据库的自动交互、数据管理工具和并行计算也将提高实验工作的有效性。所开发的算法和方法将在晶体学界广泛使用的HKL2000套件中实现。

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.