Insights into polypharmacology from drug-domain associations.

MOTIVATION: Polypharmacology (the ability of a single drug to affect multiple targets) is a key feature that may explain part of the decreasing success of conventional drug discovery strategies driven by the quest for drugs to act selectively on a single target. Most drug targets are proteins that are composed of domains (their structural and functional building blocks).
RESULTS: In this work, we model drug-domain networks to explore the role of protein domains as drug targets and to explain drug polypharmacology in terms of the interactions between drugs and protein domains. We find that drugs are organized around a privileged set of druggable domains.
CONCLUSIONS: Protein domains are a good proxy for drug targets, and drug polypharmacology emerges as a consequence of the multi-domain composition of proteins. CONTACT: amoyag@uma.es SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.