The Crystallography of Macromolecules

描述(申请人提供)：这项资助是为了推进大分子结晶学的方法及其在HKL/HKL2000项目中的实施。这将通过寻求新的统计方法和分阶段的新方法来实现。综合图形指挥中心将扩大到包括一个专家系统和自动化。这项工作的实施将扩展和改进外地最广泛使用的数据整合和缩放方案系统。这笔赠款用于： 先进的三维轮廓形状分析，这将优化信噪比，并允许部分重叠斑点的去卷积。它还将允许对从像素阵列和二极管阵列探测器获得的非常尖锐的衍射峰进行适当的建模。 开发有效的定相方法，这将通过使用非同构作为相位信息源来解决。高度冗余的测量将被用来分析和分离异常的、辐射诱导的和(可能的)其他非同构成分。将发展一种统计相移理论，以从非同构与传统相位源的建模中最佳地组合相位数。 提高方法的可靠性，重点是高通量实验，这将由一个专家系统解决，该专家系统为交互式数据收集和分析提供指导。结晶学过程各个阶段的信息含量理论将得到发展和实施。在实验过程中，对收集或模拟数据中的信息含量的正式测量将是决策过程的基础。 为了实现这些目标，我们将扩展现有的集成程序，并为未来的晶体应用开发通用的、面向对象的软件模块。这一研究和实现将提高三维大分子结构的准确性和可靠性，并将简化结构确定过程。

DESCRIPTION (provided by applicant): This grant is to advance methods of macromolecular crystallography and their implementation in the HKL/HKL2000 programs. This will be achieved by pursuing novel statistical methods and a novel approach to phasing. The integrated graphical command center will be expanded to include an expert system and automation. The implementation of this work will extend and improve the most widely used program system for data integration and scaling in the field. This grant is for: Advancing three-dimensional profile shape analysis, which will optimize the signal-to-noise ratio and allow for deconvolution of partially overlapping spots. It will also allow a proper model of the very sharp diffraction peaks obtained from pixel-array and diode-array detectors. Development of efficient phasing methods, which will be addressed by the use of non-isomorphism as a source of phase information. Highly redundant measurements will be used to analyze and separate the anomalous, radiation-induced and (potentially) other non-isomorphic components. A statistical phasing theory will be developed to optimally combine phases from modeling of non-isomorphisms with traditional sources of phases. Increasing the reliability of methods with an emphasis on high-throughput experiments, which will be addressed by an expert system that provides guidance for interactive data collection and analysis. The theory of information content for various stages of the crystallographic process will be developed and implemented. A formal measure of information content in collected or simulated data will be the basis for the decision-making process in the course of the experiment. To achieve these goals we will extend existing, integrated programs and also develop general, object oriented software modules for future crystallographic applications. The research and its implementation will increase the accuracy and reliability of 3-dimensional macromolecular structures, and will streamline the structure determination process.