Jiménez-García Brian, Pons Carles, Svergun Dmitri I, Bernadó Pau, Fernández-Recio Juan
Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona Supercomputing Center, 08034 Barcelona, Spain.
Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Nucleic Acids Res. 2015 Jul 1;43(W1):W356-61. doi: 10.1093/nar/gkv368. Epub 2015 Apr 20.
Structural characterization of protein-protein interactions at molecular level is essential to understand biological processes and identify new therapeutic opportunities. However, atomic resolution structural techniques cannot keep pace with current advances in interactomics. Low-resolution structural techniques, such as small-angle X-ray scattering (SAXS), can be applied at larger scale, but they miss atomic details. For efficient application to protein-protein complexes, low-resolution information can be combined with theoretical methods that provide energetic description and atomic details of the interactions. Here we present the pyDockSAXS web server (http://life.bsc.es/pid/pydocksaxs) that provides an automatic pipeline for modeling the structure of a protein-protein complex from SAXS data. The method uses FTDOCK to generate rigid-body docking models that are subsequently evaluated by a combination of pyDock energy-based scoring function and their capacity to describe SAXS data. The only required input files are structural models for the interacting partners and a SAXS curve. The server automatically provides a series of structural models for the complex, sorted by the pyDockSAXS scoring function. The user can also upload a previously computed set of docking poses, which opens the possibility to filter the docking solutions by potential interface residues or symmetry restraints. The server is freely available to all users without restriction.
在分子水平上对蛋白质-蛋白质相互作用进行结构表征对于理解生物过程和识别新的治疗机会至关重要。然而，原子分辨率结构技术无法跟上当前相互作用组学的进展。低分辨率结构技术，如小角X射线散射（SAXS），可以在更大规模上应用，但它们会遗漏原子细节。为了有效地应用于蛋白质-蛋白质复合物，低分辨率信息可以与提供相互作用的能量描述和原子细节的理论方法相结合。在这里，我们展示了pyDockSAXS网络服务器（http://life.bsc.es/pid/pydocksaxs），它提供了一个自动管道，用于根据SAXS数据对蛋白质-蛋白质复合物的结构进行建模。该方法使用FTDOCK生成刚体对接模型，随后通过基于pyDock能量的评分函数及其描述SAXS数据的能力进行评估。唯一需要的输入文件是相互作用伙伴的结构模型和一条SAXS曲线。服务器会自动提供一系列复合物的结构模型，并根据pyDockSAXS评分函数进行排序。用户还可以上传一组预先计算的对接姿势，这使得有可能通过潜在的界面残基或对称限制来筛选对接解决方案。该服务器对所有用户免费开放，没有限制。
