 Abstract GPCRs are master regulators of cell signalling by transducing external stimuli into the cell through selective coupling to intracellular G-proteins. This paper presents a computational analysis of the structural determinants of G-protein coupling repertoires of both experimental and predicted 3D GPCR G-protein complexes. The study found that certain structural elements such as transmembrane helices 5, 6 and interhelical loops were important for determining which type of G-protein would be coupled to the receptor. Additionally, the study showed that the G-SGPCR complexes had more conserved interfaces compared to the GIO complexes while the latter adopted a wider range of alternative docking poses. Furthermore, binding energy calculations demonstrated that distinct structural properties of the complexes were associated with higher stability of G-S than GIO complexes. Finally, the study used alpha-fold two predictions of experimental binary complexes to augment the structural coverage of polycharacterized complexes such as G-1213. This article was authored by Morin Matich, Pascuala Miglionico, Manny Tatsumi, and others. We are article.tv, links in the description below.