PROJECT 2 - MODEL COMPLETION AND VALIDATION

项目 2 - 模型完成和验证

• 批准号: 7208310
• 负责人: THOMAS C. TERWILLIGER
• 金额: $ 24.66万
• 依托单位: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7208310
• 关键词: X ray crystallography; bioengineering /biomedical engineering; biomedical automation; computational biology; computer program /software; conformation; data management; functional /structural genomics; macromolecule; mathematical model; model design /development; nucleic acid structure

As part of the PHENIX project we have developed the RESOLVE model-building algorithm, made major advances in density modification procedures, and developed rapid fitting of flexible ligands to electron density maps. We have collaborated with other members of the PHENIX project integrating these algorithms into PHENIX and to developing structure determination Wizards suitable for automated decision-making. We propose to use this foundation of algorithms and software in PHENIX as a basis for automating the completion and validation of macromolecular structures. In collaboration with project I, we will generate highly complete models at moderate resolution. In collaboration with Project IV we will develop templatematching techniques for model-building of nucleic acids. We will create a multi-model representation of the conformations of a macromolecule present in a crystal structure. We will develop our "full-omit" procedure to generate electron density maps that are highly accurate but unbiased by atomic models, and use them in validation procedures. We will develop a two-pass procedure for structure determination, a rapid pass to get a preliminary model and phases, then a second thorough pass making decisions based on correlations of phases to the model phases. We will develop PHENIX Solution objects as a framework for recording all steps carried out during structure determination, allowing repetition comprehensive deposition. We will develop systematic procedures for assessing the quality and characteristics of experimental data, maps and models. We will create a database of quality measures, decisions and their outcomes by carrying out structure determinations using PHENIX structure library and collaborate with Projects I, III and IV to develop machine-learning algorithms for decision-making in structure determination. This work will allow rapid determination and deposition of highly complete models of macromolecules and will be important for understanding biology and improving human health.

作为Phenix项目的一部分，我们开发了解决模型构建算法，使主要 密度修饰程序的进步，并将柔性配体快速拟合到电子 密度图。我们已经与Phenix项目的其他成员合作集成了这些算法 进入Phenix并开发适合自动决策的结构确定向导。 我们建议将这种算法和软件的基础作为自动化的基础 大分子结构的完成和验证。与项目I合作，我们将生成 高度完整的模型中等分辨率。与IV项目合作，我们将开发templateMutching 核酸模型建设的技术。我们将创建一个多模型表示 晶体结构中存在的大分子的构象。我们将开发我们的“全部”程序 生成高度准确但被原子模型偏见的电子密度图，并将其用于 验证程序。我们将制定一个两次通行程序来确定结构，快速通过 初步模型和阶段，然后是第二次彻底通过，根据相关性做出决定 阶段与模型阶段。我们将开发近景溶液对象作为记录所有内容的框架 在确定结构期间进行的步骤，允许重复全面沉积。我们将 制定系统的程序来评估实验数据，地图和 型号。我们将通过执行质量措施，决策及其结果的数据库 使用Phenix结构库进行结构确定，并与项目I，III和IV合作开发 用于结构确定决策的机器学习算法。这项工作将允许快速 确定和沉积高度完整的大分子模型，对于 了解生物学并改善人类健康。