The G-protein coupled receptor (GPCR) superfamily, which is comprised of estimated 600-1,000 members, is another largest known class of molecular targets with varieties of physiological activities and proven therapeutic value [103] . They are integral membrane proteins sharing a common global topology that consists of seven transmembrane alpha helices, intracellular Cterminal, an extracellular N-terminal, three intracellular loops and three extracellular loops [33, 44] . It is suggested that secondary structure and polarity would play a major role in determining the drug-GPCRs interactions activity. Small secondary structures such as helices and loops are identified as entities potentially involved in stabilizing interactions with ligands [33] . These motifs were situated mainly in the apical region of transmembrane segments and included a few extracellular residues [104] . Crystal structures of engineered human beta 2-adrenergic receptors (ARs) in complex with an inverse agonist ligand, carazolol, provide threedimensional snapshots of an important G protein-coupled receptor (GPCR) with a beta-sheet structure and forms part of the chromophore-binding site [105] . GLIDA provides interaction data between GPCRs and their ligands, along with chemical information on the ligands, as well as biological information regarding GPCRs [106] . Some of the features reflect physical interactions that are responsible for the structural stability of the transmembrane, the formation of extensive networks of interhelical H-bonds and sulfur-aromatic clusters that are spatially organized as ''polarity'', the close packing of side-chains throughout the transmembrane domain. When more experimental 3D structures become available for GPCRs in the future, this will help building reliable models for a wider range of GPCRs that would be suitable for docking studies. Joint use of ligand-based chemogenomic and docking would certainly improve the prediction.