Bioinformatics Research Centre (BiRC), Faculty of Science and Technology, Aarhus University, Denmark.
J Chem Inf Model. 2011 Apr 25;51(4):909-17. doi: 10.1021/ci100510m. Epub 2011 Mar 31.
A novel approach to incorporate water molecules in protein-ligand docking is proposed. In this method, the water molecules display the same flexibility during the docking simulation as the ligand. The method solvates the ligand with the maximum number of water molecules, and these are then retained or displaced depending on energy contributions during the docking simulation. Instead of being a static part of the receptor, each water molecule is a flexible on/off part of the ligand and is treated with the same flexibility as the ligand itself. To favor exclusion of the water molecules, a constant entropy penalty is added for each included water molecule. The method was evaluated using 12 structurally diverse protein-ligand complexes from the PDB, where several water molecules bridge the ligand and the protein. A considerable improvement in successful docking simulations was found when including flexible water molecules solvating hydrogen bonding groups of the ligand. The method has been implemented in the docking program Molegro Virtual Docker (MVD).
提出了一种将水分子纳入蛋白质-配体对接的新方法。在这种方法中，水分子在对接模拟中表现出与配体相同的灵活性。该方法用最大数量的水分子对配体进行溶剂化，然后根据对接模拟过程中的能量贡献保留或置换这些水分子。每个水分子不是受体的静态部分，而是配体的灵活开/关部分，并且与配体本身一样具有灵活性。为了有利于排除水分子，为每个包含的水分子添加一个恒定的熵罚分。该方法使用来自 PDB 的 12 个结构多样的蛋白质-配体复合物进行了评估，其中几个水分子连接配体和蛋白质。当包括可灵活的水分子来溶剂化配体的氢键基团时，发现成功对接模拟的成功率有了显著提高。该方法已在对接程序 Molegro Virtual Docker (MVD) 中实现。
