In this study, we established a pipeline to extract metal-chelating groups from structural information of ligands within metalloproteins. Here, we only focused on proteins containing Zn 2+ , Mg 2+ , and Mn 2+ , however, the pipeline is generic and can also be used to analyze ligands interacting with different metal ions. Many extracted groups contained phosphorus and are less compelling for drug discovery purposes, but others represent attractive motifs that can be pursued in the hunt for metalloprotein ligands. Further, we have investigated how well the extracted metal-chelating groups are presented in screening libraries and chemical spaces and suggested new ways on how to improve them. Together, this work will support the future discovery of inhibitors for enzymes containing Mg 2+ , Mn 2+ , or Zn 2+ in the active site as well as other metalloproteins.