G Protein-Coupled Receptors as Challenging Druggable Targets: Insights from in silico Studies

The successful identification of hundreds of G protein-coupled receptors (GPCRs) represents the single greatest opportunity for novel drug development today. The crystal structure of rhodopsin provides the first information on the three-dimensional structure of GPCRs, which now supports homology modeling studies and structure-based drug-design approaches. We review our recent work on adenosine receptors, a family of GPCRs. Focusing our attention on A3 adenosine receptor, we have demonstrated that the reciprocal integration of different theoretical and experimental disciplines can be very useful for the successful design of new, potent and selective receptor ligands.