PT  - JOURNAL ARTICLE
AU  - Aurelio A. Moya-Garcia
AU  - Natalie L. Dawson
AU  - Felix A. Kruger
AU  - John P. Overington
AU  - Christine Orengo
AU  - Juan A.G. Ranea
TI  - A Structural and Functional View of Polypharmacology
AID  - 10.1101/044289
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 044289
4099  - http://biorxiv.org/content/early/2016/03/18/044289.short
4100  - http://biorxiv.org/content/early/2016/03/18/044289.full
AB  - The similarity property principle states that similar compounds have similar properties. In this study, we demonstrate that validity this principle holds well when the drug targets are protein domains. We leverage the similarity property principle to explore the druggability of CATH-FunFams, a type of protein domain and we use the associations between drugs and CATH-FunFams to explore drug polypharmacology by considering how the drugs’ pharmacological effects arise from the molecular targets they interact with. Our results demonstrate that drug protein interactions are mediated by drug-domain interactions and that CATH-FunFams provide a reasonable annotation level for drug-target interactions, opening a new research direction in target identification.Author Summary Similar drugs tend to target the same proteins and therefore tend to have the same biological action. In this work we assess this general trend, the Similarity Property Principle, and use it to investigate the potential of CATH Functional Families, a structurally and functionally coherent protein domain definition, as drug targets. We show that the interactions between drugs and their targets are mediated by these Functional Families, and that they provide a useful mean to identify new drug targets.