Universität Hamburg , ZBH - Center for Bioinformatics , Bundesstraße 43 , 20146 Hamburg , Germany.
Bayer CropScience AG , Industriepark Hoechst G836 , 65926 Frankfurt am Main , Germany.
J Chem Inf Model. 2018 Aug 27;58(8):1625-1637. doi: 10.1021/acs.jcim.8b00271. Epub 2018 Jul 23.
Water molecules are of great importance for the correct representation of ligand binding interactions. Throughout the last years, water molecules and their integration into drug design strategies have received increasing attention. Nowadays a variety of tools are available to place and score water molecules. However, the most frequently applied software solutions require substantial computational resources. In addition, none of the existing methods has been rigorously evaluated on the basis of a large number of diverse protein complexes. Therefore, we present a novel method for placing water molecules, called WarPP, based on interaction geometries previously derived from protein crystal structures. Using a large, previously compiled, high-quality validation set of almost 1500 protein-ligand complexes containing almost 20 000 crystallographically observed water molecules in their active sites, we validated our placement strategy. We correctly placed 80% of the water molecules within 1.0 Å of a crystallographically observed one.
水分子对于正确表示配体结合相互作用非常重要。在过去的几年中，水分子及其纳入药物设计策略的工作受到了越来越多的关注。如今，有多种工具可用于放置和评分水分子。然而，最常应用的软件解决方案需要大量的计算资源。此外，现有的方法都没有基于大量不同的蛋白质复合物进行严格评估。因此，我们提出了一种新的放置水分子的方法，称为 WarPP，它基于从蛋白质晶体结构中推导出来的相互作用几何形状。我们使用一个之前编译的、高质量的验证集，该验证集包含近 1500 个蛋白质-配体复合物，这些复合物的活性部位中含有近 20000 个晶体学观察到的水分子，验证了我们的放置策略。我们正确地将 80%的水分子放置在距离晶体学观察到的水分子 1.0 Å 以内。
