1 Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark2 Department of Systems Biology, Technical University of Denmark3 University of Perugia
G-protein coupled receptors (GPCRs) are a large family of membrane-bound receptors that mediate a wide range of physiologic responses to hormones, neurotransmitters and dietary lipids, which represent an important class of drug targets. Significant chemical space regions have been explored both in the academia and by pharmaceutical companies, in the quest for new GPCR modulators as potential therapeutic agents. This accumulated body of evidence provides new opportunities to evaluate potential features of GPCR agonists and antagonists, and how to distinguish them. In this study, the chemical space covered within the WOMBAT database by GPCRs modulators was investigated with the aim of identifying specific molecular determinants that distinguish GPCR agonists from antagonists.While instrumental to get insights into the design strategies of GPCRs modulators, the results of this study provide novel clues on the molecular mechanisms that underlie the complexity of GPCR modulation.
Journal of Molecular Graphics and Modelling, 2012, Vol 38, p. 70-81
Drug design; Chemoinformatics; Structure–activity relationships; G-protein coupled receptors; Drug discovery