PROTEIN 3D STRUCTURE COMPARISON

我们已经开发了算法用于比较和 蛋白质三维结构的排列。广域(向量 对齐搜索工具)通过以下方式确定子结构相似性 比较的类型、连接性和相对方向 SSE(二级结构元素)令人惊讶的相似之处是 客观地确定，通过考虑数量和分数 最佳排列中的可叠加SSE对，以及 替代路线已采样。一种最优的逐个剩余的算法 路线也是客观地确定的，因为大多数 叠加残差和数量的惊人组合 对齐的残基。今年的工作主要集中在三个方面。这个 首先是建立一个自动增量更新系统，以 维护一个一刀切的“结构邻居”数据库 公共数据库中的域结构之间的关系。这个 庞大的邻居数据库现在包含近300万个结构 叠加路线。第二个领域是建设一个 “即时”结构的邻居服务器，目前由 结构生物学家。此服务器允许他们传输 机密坐标数据，用于与 公共结构数据库，以识别可能的远程同源基因和 将要素从一个族成员映射到另一个族成员。第三个领域 今年的工作重点是一个研究项目，旨在 区分按派生相关的结构邻居 共同的祖先基因来自那些通过融合而有亲缘关系的基因 到精力充沛的折叠图案。我们已经证明了 被称为同系物和“类似物”可能更好。 通过对HCS(同源核心结构)的测试来区分， 亚结构在先前鉴定的同系物中保守， 比之前提出的任何措施都要好。

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.