Comparative Analysis of Protein 3 Dimensional Structure

蛋白质三维结构的比较分析

• 批准号: 6554464
• 负责人: STEPHEN H. BRYANT
• 金额: --
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6554464
• 关键词: chemical information system; chemical models; computer simulation; computer system design /evaluation; conformation; information retrieval; model design /development; protein structure; statistics /biometry

We have developed algorithms for comparison and alignment of protein three dimensional structures. VAST (vector alignment search tool) identifies substructure similarities by comparing the types, connectivity, and relative orientations of SSE's (secondary structure elements). Surprising similarities are identified objectively, by considering the number and scores of superimposable SSE-pairs in the best alignment, and the number of alternative alignments sampled. An optimal residue-by-residue alignments are also identified objectively, as that with the most surprising combination of superposition residual and number of aligned residues. Work has focused in three areas. The first is construction of an automated incremental update system, to maintain an all-against-all database of the "structure neighbor" relationships among domain structures in the public database. The VAST neighbor database now contains nearly 30 million structural superpositions alignments. The second area is construction of an "on-the-fly" structure neighbor server, which is now in use by structural biologists. This server allows them to transmit confidential coordinate data for VAST comparison against the public structure database, to identify possible remote homologs and to map features from one family member to another. The third area of work this year has been a research project aimed at distinguishing structure neighbors that are related by descent from a common ancestral gene from those that are related by convergence to energetically preferred folding motifs. We have shown that homologs and "analogs", as they have been called, may be better distinguished by a test for the HCS (Homologous Core Structure), the substructure conserved among previously identified homologs, than by any measures proposed earlier. Research is in progress to fully automate HCS calculations, and to construct multiple structure alignments of homologous protein domains as clustered by HCS overlap.

我们已经开发了蛋白质三维结构的比较和比对算法。VAST（矢量比对搜索工具）通过比较SSE（二级结构元素）的类型、连接性和相对方向来识别子结构相似性。通过考虑最佳比对中可重叠SSE对的数量和分数以及采样的替代比对的数量，客观地识别出令人惊讶的相似性。一个最佳的残基的残基比对也被客观地确定，作为最令人惊讶的组合的叠加残差和对齐的残基的数量。工作集中在三个领域。第一个是建立一个自动增量更新系统，以维护公共数据库中域结构之间的“结构邻居”关系的所有对所有数据库。VAST邻居数据库现在包含近3000万个结构叠加对齐。第二个领域是构建一个“在飞”结构邻居服务器，这是现在使用的结构生物学家。该服务器使他们能够传输机密的坐标数据，用于与公共结构数据库进行VAST比较，以确定可能的远程同源物，并将一个家庭成员的特征映射到另一个家庭成员。今年的第三个工作领域是一个研究项目，旨在区分与共同祖先基因有血缘关系的结构邻居和与能量偏好折叠基序有趋同关系的结构邻居。我们已经表明，同源物和“类似物”，因为他们已经被称为，可能会更好地区分HCS（同源核心结构），子结构之间的保守先前确定的同源物，比任何措施提出较早的测试。研究正在进行中，以完全自动化HCS计算，并构建同源蛋白质结构域的多个结构比对，如通过HCS重叠聚类的。