Weinhold Nils, Sander Oliver, Domingues Francisco S, Lengauer Thomas, Sommer Ingolf
Max Planck Institute for Informatics, Saarbrücken, Germany.
PLoS Comput Biol. 2008 Jul 4;4(7):e1000105. doi: 10.1371/journal.pcbi.1000105.
We assess the variability of protein function in protein sequence and structure space. Various regions in this space exhibit considerable difference in the local conservation of molecular function. We analyze and capture local function conservation by means of logistic curves. Based on this analysis, we propose a method for predicting molecular function of a query protein with known structure but unknown function. The prediction method is rigorously assessed and compared with a previously published function predictor. Furthermore, we apply the method to 500 functionally unannotated PDB structures and discuss selected examples. The proposed approach provides a simple yet consistent statistical model for the complex relations between protein sequence, structure, and function. The GOdot method is available online (http://godot.bioinf.mpi-inf.mpg.de).
我们评估了蛋白质序列和结构空间中蛋白质功能的变异性。该空间中的各个区域在分子功能的局部保守性方面表现出相当大的差异。我们通过逻辑曲线分析并捕捉局部功能保守性。基于此分析，我们提出了一种预测具有已知结构但未知功能的查询蛋白质分子功能的方法。对该预测方法进行了严格评估，并与先前发表的功能预测器进行了比较。此外，我们将该方法应用于500个功能未注释的PDB结构，并讨论了选定的示例。所提出的方法为蛋白质序列、结构和功能之间的复杂关系提供了一个简单而一致的统计模型。GOdot方法可在线获取（http://godot.bioinf.mpi-inf.mpg.de）。
