GPDOCK: highly accurate docking strategy for metalloproteins based on geometric probability

Abstract Accurately predicting the interaction modes for metalloproteins remains extremely challenging in structure-based drug design and mechanism analysis of enzymatic catalysis due to the complexity of metal coordination in metalloproteins. Here, we report a docking method for metalloproteins based on geometric probability (GPDOCK) with unprecedented accuracy. The docking tests of 10 common metal ions with 9360 metalloprotein–ligand complexes demonstrate that GPDOCK has an accuracy of 94.3% in predicting binding pose. What is more, it can accurately realize the docking of metalloproteins with ligand when one or two water molecules are engaged in the metal ion coordination. Since GPDOCK only depends on the three-dimensional structure of metalloprotein and ligand, structure-based machine learning model is employed for the scoring of binding poses, which significantly improves computational efficiency. The proposed docking strategy can be an effective and efficient tool for drug design and further study of binding mechanism of metalloproteins. The manual of GPDOCK and the code for the logistical regression model used to re-rank the docking results are available at https://github.com/wangkai-zhku/GPDOCK.git.