PROTEIN 3D STRUCTURE COMPARISON

蛋白质 3D 结构比较

• 批准号: 6111066
• 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/6111066
• 关键词: chemical information system; chemical models; computer data analysis; computer program /software; conformation; information retrieval; information system analysis; 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 this year 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 3 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.

我们已经开发了用于比较的算法， 蛋白质三维结构的排列。VAST（矢量 对齐搜索工具）通过以下方式识别子结构相似性 比较的类型，连通性，和相对方向， 二级结构元素（Secondary Structure Elements）令人惊讶的相似之处是 客观地确定，通过考虑的数量和分数， 最佳比对中的可重叠SSE对，以及 抽样的备选路线。最优逐残法 路线也是客观确定的，因为最 令人惊讶的组合叠加残差和数量的 对齐的残基。今年的工作集中在三个方面。的 一是建立自动化增量更新系统， 维护“结构邻居”的所有对所有数据库 公共数据库中的域结构之间的关系。的 VAST邻居数据库现在包含近300万个结构 叠加对齐。第二个领域是建设一个 “动态”结构邻居服务器，现在由 结构生物学家这个服务器允许他们传输 用于VAST对比的机密坐标数据 公共结构数据库，以确定可能的远程同源物， 将特征从一个家庭成员映射到另一个家庭成员。第三区域 今年的工作是一个研究项目，旨在 区分结构邻居是相关的血统，从一个 从那些因趋同而相关的基因中分离出来的共同祖先基因 到能量优先的折叠图案。我们已经证明 同源物和“类似物”，因为它们被称为，可能更好， 通过对HCS（Homestead Core Structure）的测试来区分， 该亚结构在先前鉴定的同源物中保守， 而不是之前提出的任何措施。