G protein-coupled receptors: computer-aided ligand discovery and computational structural analyses in the 2010s.

G protein-coupled receptors, or GPCRs, are a large superfamily of proteins found on the plasma membrane of cells. They are involved in most physiological and pathophysiological functions and constitute the target of the majority of marketed drugs. Although these receptors have been historically elusive to attempts of structural determination, GPCR crystallography is now in full blossom, opening the way to structure-based drug discovery and enabling homology modeling. This thematic issue of the journal In Silico Pharmacology, which illustrates how the expanding body of structural knowledge is fostering complex computational analyses of the structure-function relationships of the receptors and their interactions with their ligands, stems from the 31st Camerino-Cyprus-Noordwijkerhout Symposium held in Italy, in May 2013, at the University of Camerino. Specifically, it originates from a session of the symposium entitled "Structure-Based Discovery of Ligands of G Protein-Coupled Receptors: Finally a Reality", and features a mix of research articles and reviews on the application of computational modeling to the analysis of the structure of GPCRs and the interactions of the receptors with their ligands.