Ranking models of transmembrane β-barrel proteins using Z-coordinate predictions
Ranking models of transmembrane β-barrel proteins using Z-coordinate predictions
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DOI：
10.1093/bioinformatics/bts233
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发表时间：
2012-06-15
期刊：
影响因子：
5.8
通讯作者：
Elofsson, Arne
中科院分区：
文献类型：
--
作者：
Hayat, Sikander;Elofsson, Arne
动机：跨膜β-桶存在于革兰氏阴性菌的外膜以及叶绿体和线粒体中。它们通常参与转运过程，是有前途的抗微生物药物靶点。只有少数β桶蛋白家族的结构是已知的。因此，能够自动生成这种模型的方法将是有价值的。桶的对称排列表明，基于理想化的几何形状的方法可能是success.Results：在这里，我们提出了一种新的模型，用于生成β-桶跨膜蛋白的3D模型的方法。首先，从BOCTOPUS拓扑预测器获得替代拓扑。此后，通过使用不同角度的β-片层构建几个3D模型。最后，基于与新预测器ZPRED 3的一致性来选择最佳模型，该预测器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 A。Tobmodel预测了数据集中75%的蛋白质的正确拓扑结构，这比单独使用BOCTOPUS略有改进。然而，更重要的是，RISK模型提供了一个C α模板，其与天然结构的平均RMSD为7.24 A。
Motivation: Transmembrane beta-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 beta-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.Results: Here, we present tobmodel; a method for generating 3D models of beta-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 beta-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 A. 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 C alpha template with an average RMSD of 7.24 A from the native structure.