Physicochemical properties of GPCR amino acid sequences for understanding GPCR-G-protein coupling

G-protein coupled receptors (GPCRs) bind with G-proteins upon activation by ligands. Understanding the mechanisms of specific binding between GPCRs and G-proteins is one of the most important issues in bioinformatics research. In this study, the physical properties of various regions were analyzed in order to classify GPCRs by G-protein family and to better understand binding specificity. We focused on cytoplasmic loops (IL1, IL2 and N/C-terminus of IL3), extracellular loops (NTL, EL1 and N/C-terminus of EL2) and cytoplasmic termini of transmembrane helices, except for helices that connect to C-terminus loops. The distribution of hydrophobicity, charge density, lysine and arginine densities, and loop length enabled discrimination of GPCRs with more than 90% accuracy.