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: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: Amines are biogenic amino acid derivatives, which play pleiotropic and very important yet complex roles in animal physiology. For many other relevant biomolecules, biochemical and molecular data are being accumulated, which need to be integrated in order to be effective in the advance of biological knowledge in the field. For this purpose, a multidisciplinary group has started an ontology-based system named the Amine System Project (ASP) for which amine-related information is the validation bench. RESULTS: In this paper, we describe the Ontology-Based Mediator developed in the Amine System Project (http://asp.uma.es) using the infrastructure of Semantic Directories, and how this system has been used to solve a case related to amine metabolism-related protein structures. CONCLUSIONS: This infrastructure is used to publish and manage not only ontologies and their relationships, but also metadata relating to the resources committed with the ontologies. The system developed is available at http://asp.uma.es/WebMediator.