PROTEIN 3D STRUCTURE COMPARISON

我们已经开发了比较和排列蛋白质三维结构的算法。VAST（矢量比对搜索工具）通过比较sse（二级结构元素）的类型、连通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的sse对的数量和分数，以及抽样的备选比对的数量，客观地确定了惊人的相似性。最优残基对残基比对也被客观地确定为最令人惊讶的叠加残基和对齐残基数目的组合。今年的工作主要集中在三个方面。首先是构建自动增量更新系统，维护公共数据库中领域结构间结构邻居关系的全对抗数据库。VAST邻居数据库现在包含近300万个结构叠加排列。第二个领域是构建一个动态的结构邻居服务器，它现在被结构生物学家使用。该服务器允许他们传输机密坐标数据，以便与公共结构数据库进行VAST比较，以识别可能的远程同源物，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，旨在区分那些与共同祖先基因的血统有关的结构邻居和那些与能量优先折叠基序的收敛有关的结构邻居。我们已经证明，通过HCS（同源核心结构）的测试可以更好地区分同源物和类似物，HCS（同源核心结构）是先前确定的同源物中保守的亚结构，而不是之前提出的任何方法。研究正在进行中，以完全自动化HCS计算，并构建同源蛋白结构域的多个结构比对，如HCS重叠聚集。-蛋白质三维结构比较同源核心结构-既不是人体受试者也不是人体组织

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 SSEs (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. Research is in progress to fully automate HCS calculations, and to construct multiple structure alignments of homologous protein domains as clustered by HCS overlap. - protein 3D structure comparison homologous core structure - Neither Human Subjects nor Human Tissues