Schematic overview of the methodology. A) The contacting domains per family are extracted from the SCOWLP database. The Si are calculated for all-against-all contacting domains and used for clustering. Results are displayed in a dendrogram. B) Classification of protein binding regions (PBRs). A protein family can recognize other proteins and ligands by single- or multi-binding regions, and for each binding region single- or multi-interfaces may exist depending on the number of partners that have been structurally observed interacting within a specific binding region.