Structural and Functional View of Polypharmacology

Protein domains mediate drug-protein interactions and this effect can explain drug polypharmacology. In this study, we associate polypharmacological drugs with CATH functional families, a type of protein domain and we use the network properties of these druggable protein families to analyse their relationships with drug side effects. We found druggable CATH functional families enriched in drug targets, whose relatives are structurally coherent, gather together in the protein functional network occupying central positions, and tend to be free of proteins associated with drug side effects. Our results demonstrate that CATH functional families can be used to identify drug-target interactions, opening a new research direction in target identification.