The Crystallography of Macromolecules

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水平信息的巨大需求导致了大规模的实验努力，晶体学是其主要技术。该基金的目的是在数据收集、衍射峰积分、缩放和合并等领域改进晶体衍射数据分析方法。这些方法既适用于晶体学的主流用途，也适用于晶体学的前沿领域。改进的核心，目前的方法将导致从精确建模的衍射峰的形状，去除衍射伪影，辐射损伤引起的影响和更好的诊断可能的问题，如伪对称性和/或孪生等具有挑战性的结构项目需要复杂的优化结晶和低温保护条件的校正。如果可能的话，这些项目可以从多个晶体的平均数据中受益匪浅，到目前为止，由于缺乏适当的工具，大多数情况下都是避免的。我们计划开发一种新型的衍射信号分析，将比较来自多个晶体的数据，以确定其衍射质量和一致性。来自多个晶体的数据将被分解成统计上显著的信号，包括所需的定相信号和非同构的描述。这种分析的结果将是直接的解释和最佳的平均数据方面，不一定完全同晶晶体。这一发展尤其重要，因为该技术扩大了晶体的生产和衍射数据的收集。实验工作效率的提高还将得益于扩展的实验规划工具、与外部数据库的自动交互、数据管理工具和并行计算。所开发的算法和方法将在HKL 2000套件中实现，该套件被晶体学界广泛使用。

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.