Ward R Matthew, Venner Eric, Daines Bryce, Murray Stephen, Erdin Serkan, Kristensen David M, Lichtarge Olivier
Department of Molecular and Human Genetics, Program in Structural and Computational Biology and Molecular, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Bioinformatics. 2009 Jun 1;25(11):1426-7. doi: 10.1093/bioinformatics/btp160. Epub 2009 Mar 23.
The Evolutionary Trace Annotation (ETA) Server predicts enzymatic activity. ETA starts with a structure of unknown function, such as those from structural genomics, and with no prior knowledge of its mechanism uses the phylogenetic Evolutionary Trace (ET) method to extract key functional residues and propose a function-associated 3D motif, called a 3D template. ETA then searches previously annotated structures for geometric template matches that suggest molecular and thus functional mimicry. In order to maximize the predictive value of these matches, ETA next applies distinctive specificity filters -- evolutionary similarity, function plurality and match reciprocity. In large scale controls on enzymes, prediction coverage is 43% but the positive predictive value rises to 92%, thus minimizing false annotations. Users may modify any search parameter, including the template. ETA thus expands the ET suite for protein structure annotation, and can contribute to the annotation efforts of metaservers.
The ETA Server is a web application available at (http://mammoth.bcm.tmc.edu/eta/).
进化追踪注释（ETA）服务器可预测酶活性。ETA以功能未知的结构（如来自结构基因组学的结构）为起始，在对其作用机制毫无先验知识的情况下，使用系统发育进化追踪（ET）方法提取关键功能残基，并提出一个与功能相关的3D基序，称为3D模板。然后，ETA在先前注释的结构中搜索几何模板匹配项，这些匹配项暗示分子模拟进而功能模拟。为了使这些匹配的预测价值最大化，ETA接下来应用独特的特异性筛选标准——进化相似性、功能多样性和匹配互反性。在对酶的大规模控制中，预测覆盖率为43%，但阳性预测值上升到92%，从而将错误注释降至最低。用户可以修改任何搜索参数，包括模板。因此，ETA扩展了用于蛋白质结构注释的ET套件，并可为元服务器的注释工作做出贡献。
ETA服务器是一个网络应用程序，可通过（http://mammoth.bcm.tmc.edu/eta/）访问。
