Predicting ligands for orphan GPCRs

G-protein-coupled receptors (GPCRs) represent not only one of the most successful target classes for the pharmaceutical industry, but also one of the largest and most structurally and functionally diverse. Many are 'orphan' GPCRs that have not yet been paired with their cognate ligands. Computational approaches are well suited for this type of classification problem, but most are confounded when the orphan is dissimilar to characterized GPCRs.