Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm Bioinformatics Center, Science for Life Laboratory, Swedish E-science Research Center, Stockholm University, SE-10691 Stockholm, Sweden.
Bioinformatics. 2012 Jun 15;28(12):i90-6. doi: 10.1093/bioinformatics/bts233.
Transmembrane β-barrels exist in the outer membrane of gram-negative bacteria as well as in chloroplast and mitochondria. They are often involved in transport processes and are promising antimicrobial drug targets. Structures of only a few β-barrel protein families are known. Therefore, a method that could automatically generate such models would be valuable. The symmetrical arrangement of the barrels suggests that an approach based on idealized geometries may be successful.
Here, we present tobmodel; a method for generating 3D models of β-barrel transmembrane proteins. First, alternative topologies are obtained from the BOCTOPUS topology predictor. Thereafter, several 3D models are constructed by using different angles of the β-sheets. Finally, the best model is selected based on agreement with a novel predictor, ZPRED3, which predicts the distance from the center of the membrane for each residue, i.e. the Z-coordinate. The Z-coordinate prediction has an average error of 1.61 Å. Tobmodel predicts the correct topology for 75% of the proteins in the dataset which is a slight improvement over BOCTOPUS alone. More importantly, however, tobmodel provides a Cα template with an average RMSD of 7.24 Å from the native structure.
Tobmodel is freely available as a web server at: http://tobmodel.cbr.su.se/. The datasets used for training and evaluations are also available from this site.
跨膜β-桶存在于革兰氏阴性细菌的外膜以及叶绿体和线粒体中。它们通常参与运输过程，是有前途的抗菌药物靶点。目前仅知道少数几种β-桶蛋白家族的结构。因此，能够自动生成此类模型的方法将是有价值的。桶的对称排列表明，基于理想化几何形状的方法可能会成功。
在这里，我们提出了 tobmodel；一种生成β-桶跨膜蛋白 3D 模型的方法。首先，从 BOCTOPUS 拓扑预测器获得替代拓扑。此后，通过使用不同的β-片角度来构建多个 3D 模型。最后，根据与新的 ZPRED3 预测器的一致性选择最佳模型，ZPRED3 预测每个残基距膜中心的距离，即 Z 坐标。Z 坐标预测的平均误差为 1.61 Å。tobmodel 预测数据集内 75%的蛋白质具有正确的拓扑结构，这比单独使用 BOCTOPUS 略有改进。然而，更重要的是，tobmodel 提供了一个 Cα模板，与天然结构的 RMSD 平均值为 7.24 Å。
tobmodel 可作为一个免费的网络服务器在 http://tobmodel.cbr.su.se/ 上使用。用于训练和评估的数据集也可从该网站获得。
