The Crystallography of Macromolecules

高分子晶体学

• 批准号: 6891845
• 负责人: ZBYSZEK OTWINOWSKI
• 金额: $ 43.32万
• 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 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6891845
• 关键词: X ray crystallography; automated data processing; bioimaging /biomedical imaging; computer human interaction; computer system design /evaluation; high throughput technology; information theory; macromolecule; method development; model design /development; physical model; protein structure function; radiochemistry; statistics /biometry; thermodynamics; three dimensional imaging /topography

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.

描述（由申请人提供）：这笔赠款是为了推进大分子晶体学及其在HKL/HKL2000程序中的实现方法。这将通过追求新颖的统计方法和一种新颖的方法来实现。集成图形指挥中心将扩展到包括专家系统和自动化。这项工作的实施将扩展并改善最广泛使用的数据集成和缩放的程序系统。这笔赠款是为： 推进三维轮廓形状分析，这将优化信噪比，并允许部分重叠点的反卷积。它还将允许从像素阵列和二极管阵列探测器获得的非常清晰的衍射峰的正确模型。 开发有效的相位方法，将通过使用非同态性作为相信息来源来解决。高度冗余的测量将用于分析和分离异常的，辐射诱导的和（可能）其他非同构成分。将开发出统计分阶段理论，以最佳地结合非同态建模与传统阶段来源的相结合。 提高方法的可靠性，重点是高通量实验，这将由专家系统解决，该系统为交互式数据收集和分析提供指导。将开发和实施晶体学过程各个阶段的信息内容理论。在实验过程中，收集或模拟数据中信息内容的正式度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，集成的程序，并为未来的晶体学应用程序开发一般面向对象的软件模块。该研究及其实施将提高3维大分子结构的准确性和可靠性，并将简化结构确定过程。