Automated X-ray Crystallography for Structural Genomics

用于结构基因组学的自动 X 射线晶体学

• 批准号: 6769435
• 负责人: PAUL David ADAMS
• 金额: $ 144.48万
• 依托单位: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6769435
• 关键词: X ray crystallography; bioengineering /biomedical engineering; bioimaging /biomedical imaging; biomedical automation; computer program /software; mathematical model; model design /development; protein structure function; proteomics; structural biology

Structural genomics seeks to rapidly expand the database of protein structures to permit the extract8on of much more information from the genomic sequence databases than is currently possible. This requires methods for the rapid determination of macromolecular structures using X-ray crystallography. At present the need for continual manual intervention makes rapid, minimally biased structure solution impossible. Therefore, it is imperative that crystallographic structure determination be automated in the near future. Unfortunately the crystallographic packages currently available, although possessing many powerful features, are collectively too diverse, out-data and lacking in the required functionality to be used as a solution to the problem. Major bottlenecks remain, especially during the process of model building and refinement. Therefore we will build a new system for crystallographic computing that will allow, amongst other things, the creation of new software that combines the powerful automation features of the SOLVE system, the computational flexibility of the Crystallography & NMR System and the automated map interpretation algorithms of the TEXTAL program. This system, named PHENIX, will permit tasks required for the computation of phases, automated map interpretation, model building and refinement, to be integrated with newly developed procedures for automated decision-making. Our ultimate goal is the development of a system that will take x-ray diffraction data and rapidly procedure biased atomic coordinates with little or no human intervention. The advantages of such a system extend beyond the realm of structural, genomics, allowing crystallographers to focus on more challenging biological problems.

结构性基因组学旨在快速扩展蛋白质结构的数据库，以允许从基因组序列数据库中更多信息的提取物进行超过目前的可能性。这需要使用X射线晶体学快速测定大分子结构的方法。目前，需要连续手动干预使快速，最小偏见的结构解决方案不可能。因此，必须在不久的将来对晶体结构的确定进行自动化。不幸的是，尽管拥有许多强大的功能，但目前可用的晶体学软件包集体过于多样，超数据，并且缺乏所需的功能，无法用作解决问题的解决方案。仍然存在主要的瓶颈，尤其是在模型建设和改进过程中。因此，我们将构建一个用于晶体学计算的新系统，除其他外，还可以创建新软件，该软件结合了Solve系统的强大自动化功能，晶体学和NMR系统的计算灵活性以及自动化的文本图表解释算法。该系统名为Phenix，将允许计算阶段，自动化地图解释，模型构建和改进所需的任务，并与新开发的自动决策过程集成在一起。我们的最终目标是开发一个系统，该系统将获取X射线衍射数据，并迅速进行原子坐标，几乎没有人为干预。这种系统的优势超出了结构性，基因组学的范围，使晶体学家能够专注于更具挑战性的生物学问题。