Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment and The Fritz Haber Center for Molecular Dynamics, The Hebrew University, Rehovot 76100, Israel.
Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment and The Fritz Haber Center for Molecular Dynamics, The Hebrew University, Rehovot 76100, Israel.
Structure. 2015 May 5;23(5):929-940. doi: 10.1016/j.str.2015.03.010. Epub 2015 Apr 23.
The huge conformational space stemming from the inherent flexibility of peptides is among the main obstacles to successful and efficient computational modeling of protein-peptide interactions. Current peptide docking methods typically overcome this challenge using prior knowledge from the structure of the complex. Here we introduce AnchorDock, a peptide docking approach, which automatically targets the docking search to the most relevant parts of the conformational space. This is done by precomputing the free peptide's structure and by computationally identifying anchoring spots on the protein surface. Next, a free peptide conformation undergoes anchor-driven simulated annealing molecular dynamics simulations around the predicted anchoring spots. In the challenging task of a completely blind docking test, AnchorDock produced exceptionally good results (backbone root-mean-square deviation ≤ 2.2Å, rank ≤15) for 10 of 13 unbound cases tested. The impressive performance of AnchorDock supports a molecular recognition pathway that is driven via pre-existing local structural elements.
肽的固有灵活性所产生的巨大构象空间是成功和有效地进行蛋白质-肽相互作用的计算建模的主要障碍之一。当前的肽对接方法通常使用复合物结构的先验知识来克服这一挑战。在这里，我们介绍了 AnchorDock，这是一种肽对接方法，它可以自动将对接搜索定位到构象空间中最相关的部分。这是通过预先计算游离肽的结构并在蛋白质表面上计算识别锚固点来实现的。接下来，一个游离肽构象在预测的锚固点周围进行锚定驱动的模拟退火分子动力学模拟。在完全盲目的对接测试这一具有挑战性的任务中，AnchorDock 在 13 个未结合的案例中产生了 10 个非常好的结果（骨架均方根偏差≤2.2Å，排名≤15）。AnchorDock 的出色表现支持了一种分子识别途径，该途径是通过预先存在的局部结构元素驱动的。
