SCOP: A Revitalized Foundation for Studies of Protein Structure and Evolution

说明(由申请人提供)：项目摘要/摘要本项目的主要目标将是振兴蛋白质结构分类(SCOP)和Astral数据库，以便更好地服务于当前用户和更大的科学界的需要。这两个数据库都提供了经过精心管理的资源，生物学家广泛使用这些资源来探索感兴趣的蛋白质的远程同源基因，计算生物学家则将其作为基准预测算法的“黄金标准”。然而，自早期版本以来，这两个数据库都没有改变其基本设计--以SCOP为例是在15年前。我们将重新设计这两个数据库的内部结构，以考虑在最初创建数据库时没有意识到的蛋白质进化方面，例如进化出不同折叠的变质蛋白质和同源蛋白质。我们还将开发一个到这两个数据库的统一接口，使科学家能够轻松地找到并专注于感兴趣的蛋白质或家族，因为随着更多结构的添加，当前的分级视图变得越来越笨拙。由于今天要解决大量的结构，SCOP的整理过程已经成为一个瓶颈，我们计划建立自动化工具来帮助分类。我们还将创建界面，允许生物学家提交序列或结构，以便使用后一种工具进行自动分类。在许多情况下，这将使结构生物学家在公布新解决的结构之前，对蛋白质的进化或功能有更深入的了解。 公共卫生相关性： 项目简介SCOP和Astral数据库是经过精心管理的资源，生物学家广泛使用它们来探索感兴趣的蛋白质家族的结构、功能和进化，计算生物学家将其作为基准预测算法的“黄金标准”。蛋白质结构对许多病原体和人类疾病的现代研究至关重要，而医疗条件正迅速与特定的突变联系在一起。尽管结构信息的洪流威胁着我们目前的分析能力，但我们建议对SCOP和Astral的管理程序进行更改，并改进数据库的底层结构，将使这些资源在未来许多年继续产生生物学和医学洞察力。

DESCRIPTION (provided by applicant): Project Summary/Abstract The primary goal of this project will be to revitalize the Structural Classification of Proteins (SCOP) and ASTRAL databases, both in order to better serve the needs of both current users and the larger scientific community. Both databases provide carefully curated resources that are widely used by biologists to explore remote homologs of proteins of interest, and by computational biologists as a "gold standard" for benchmarking prediction algorithms. However, neither database has changed its basic design since early releases-15 years ago in the case of SCOP. We will redesign the internals of both databases in order to account for aspects of protein evolution that were not appreciated at the time the databases were first created, such as metamorphic proteins and homologous proteins that have evolved different folds. We will also develop a unified interface to both databases that will allow scientists to easily find and focus on proteins or families of interest, as the current hierarchical view is increasingly unwieldy as more structures are added. Since the process of SCOP curation has become a bottleneck due to the large number of structures being solved today, we plan to build automated tools to assist in the classification. We will also create interfaces to allow biologists to submit sequences or structures for automated classification using the latter tools. In many cases, this would enable structural biologists to gain insight into a protein's evolution or function prior to publication of a newly solved structure. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE The SCOP and ASTRAL databases are carefully curated resources that are widely used by biologists to explore the structure, function, and evolution of protein families of interest, and by computational biologists as a "gold standard" for benchmarking prediction algorithms. Protein structures are essential to many modern studies of pathogens and human diseases, and medical conditions are being rapidly linked to specific mutations. Although the flood of structural information threatens to overwhelm our current capacity for analysis, our proposed changes to the curation procedures for SCOP and ASTRAL, and improvements to the underlying structure of the databases, will allow these resources to continue to yield biological and medical insight for many years to come.