Schindler Christina, Zacharias Martin
Physics Department (T38), Center for Integrated Protein Science Munich (CIPSM), Technical University of Munich, James-Franck-Str. 1, 85748, Garching, Germany.
Methods Mol Biol. 2017;1561:49-68. doi: 10.1007/978-1-4939-6798-8_5.
Peptide-protein interactions are abundant in the cell and form an important part of the interactome. Large-scale modeling of peptide-protein complexes requires a fully blind approach; i.e., simultaneously predicting the peptide-binding site and the peptide conformation to high accuracy. Here, we present one of the first fully blind peptide-protein docking protocols, pepATTRACT. It combines a coarse-grained ensemble docking search of the entire protein surface with two stages of atomistic flexible refinement. pepATTRACT yields high-quality predictions for 70 % of the cases when tested on a large benchmark of peptide-protein complexes. This performance in fully blind mode is similar to state-of-the-art local docking approaches that use information on the location of the binding site. Limiting the search to the peptide-binding region, the resulting pepATTRACT-local approach further improves the performance. Docking scripts for pepATTRACT and pepATTRACT-local can be generated via a web interface at www.attract.ph.tum.de/peptide.html . Here, we explain how to set up a docking run with the pepATTRACT web interface and demonstrate its usage by an application on binding of disordered regions from tumor suppressor p53 to a partner protein.
肽 - 蛋白质相互作用在细胞中广泛存在，是相互作用组的重要组成部分。肽 - 蛋白质复合物的大规模建模需要一种完全盲目的方法，即同时高精度地预测肽结合位点和肽构象。在此，我们展示了首个完全盲目的肽 - 蛋白质对接协议之一，pepATTRACT。它将对整个蛋白质表面的粗粒度整体对接搜索与两个原子级柔性优化阶段相结合。在对大量肽 - 蛋白质复合物基准进行测试时，pepATTRACT在70%的情况下能产生高质量预测。在完全盲目的模式下，这种性能与使用结合位点位置信息的最先进局部对接方法相似。将搜索限制在肽结合区域，由此产生的pepATTRACT - local方法进一步提高了性能。可通过www.attract.ph.tum.de/peptide.html的网络界面生成pepATTRACT和pepATTRACT - local的对接脚本。在此，我们解释如何使用pepATTRACT网络界面设置对接运行，并通过应用肿瘤抑制因子p53的无序区域与一种伴侣蛋白的结合来展示其用法。
