| Autor: |
Moya-García A; University College London, Institute of Structural and Molecular Biology, London, UK. aurelio.moya@ucl.ac.uk.; Department of Molecular Biology and Biochemistry, Universidad de Malaga, 29071, Málaga Spain, CIBER de Enfermedades Raras (CIBERER), 29071, Málaga, Spain. aurelio.moya@ucl.ac.uk., Adeyelu T; University College London, Institute of Structural and Molecular Biology, London, UK., Kruger FA; European Molecular Laboratory - European Bioinformatics Institute, Hinxton, UK.; BenevolentAI, Churchway 40, NW1 1LW, London, UK., Dawson NL; University College London, Institute of Structural and Molecular Biology, London, UK., Lees JG; University College London, Institute of Structural and Molecular Biology, London, UK., Overington JP; European Molecular Laboratory - European Bioinformatics Institute, Hinxton, UK.; Medicines Discovery Catapult, Mereside, Alderley Park, Alderley Edge, Cheshire, SK10 4TG, UK., Orengo C; University College London, Institute of Structural and Molecular Biology, London, UK., Ranea JAG; Department of Molecular Biology and Biochemistry, Universidad de Málaga, 29071, Málaga, Spain.; CIBER de Enfermedades Raras (CIBERER), 29071, Málaga, Spain. |
| Abstrakt: |
Protein domains mediate drug-protein interactions and this principle can guide the design of multi-target drugs i.e. polypharmacology. In this study, we associate multi-target drugs with CATH functional families through the overrepresentation of targets of those drugs in CATH functional families. Thus, we identify CATH functional families that are currently enriched in drugs (druggable CATH functional families) and we use the network properties of these druggable protein families to analyse their association with drug side effects. Analysis of selected druggable CATH functional families, enriched in drug targets, show that relatives exhibit highly conserved drug binding sites. Furthermore, relatives within druggable CATH functional families occupy central positions in a human protein functional network, cluster together forming network neighbourhoods and are less likely to be within 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. |
