Amela Isaac, Delicado Pedro, Gómez Antonio, Bonàs Sílvia, Querol Enrique, Cedano Juan
Institut de Biotecnologia i de Biomedicina Parc de Recerca UAB, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain.
BMC Struct Biol. 2010 Oct 22;10:37. doi: 10.1186/1472-6807-10-37.
Is it possible to identify what the best solution of a docking program is? The usual answer to this question is the highest score solution, but interactions between proteins are dynamic processes, and many times the interaction regions are wide enough to permit protein-protein interactions with different orientations and/or interaction energies. In some cases, as in a multimeric protein complex, several interaction regions are possible among the monomers. These dynamic processes involve interactions with surface displacements between the proteins to finally achieve the functional configuration of the protein complex. Consequently, there is not a static and single solution for the interaction between proteins, but there are several important configurations that also have to be analyzed.
To extract those representative solutions from the docking output datafile, we have developed an unsupervised and automatic clustering application, named DockAnalyse. This application is based on the already existing DBscan clustering method, which searches for continuities among the clusters generated by the docking output data representation. The DBscan clustering method is very robust and, moreover, solves some of the inconsistency problems of the classical clustering methods like, for example, the treatment of outliers and the dependence of the previously defined number of clusters.
DockAnalyse makes the interpretation of the docking solutions through graphical and visual representations easier by guiding the user to find the representative solutions. We have applied our new approach to analyze several protein interactions and model the dynamic protein interaction behavior of a protein complex. DockAnalyse might also be used to describe interaction regions between proteins and, therefore, guide future flexible dockings. The application (implemented in the R package) is accessible.
能否确定对接程序的最佳解决方案是什么？这个问题通常的答案是得分最高的解决方案，但蛋白质之间的相互作用是动态过程，而且很多时候相互作用区域足够宽，允许蛋白质以不同的方向和/或相互作用能量进行蛋白质-蛋白质相互作用。在某些情况下，如在多聚体蛋白质复合物中，单体之间可能存在多个相互作用区域。这些动态过程涉及与蛋白质之间表面位移的相互作用，最终实现蛋白质复合物的功能构型。因此，蛋白质之间的相互作用不存在静态且单一的解决方案，而是有几个重要的构型也需要进行分析。
为了从对接输出数据文件中提取那些具有代表性的解决方案，我们开发了一个无监督自动聚类应用程序，名为DockAnalyse。该应用程序基于现有的DBSCAN聚类方法，该方法在对接输出数据表示生成的聚类中搜索连续性。DBSCAN聚类方法非常稳健，而且解决了一些经典聚类方法的不一致问题，例如异常值的处理以及预先定义的聚类数量的依赖性。
DockAnalyse通过引导用户找到具有代表性的解决方案，使通过图形和可视化表示对接解决方案的解释变得更加容易。我们已经应用我们的新方法来分析几种蛋白质相互作用，并对蛋白质复合物的动态蛋白质相互作用行为进行建模。DockAnalyse还可用于描述蛋白质之间的相互作用区域，因此可指导未来的灵活对接。该应用程序（在R包中实现）是可访问的。
