Knowledge Bank

The purpose of the first part of this study is to computationally model theoretical the three-dimensional structures of proteins that interact with cannabinoids. The synthetic cannabinoids, THC and CBD, can interact with G-protein couple receptors (GPCRs). Their primary targets are cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). A potential cannabinoid receptor 3 (CB3), which is known as the cannabinoid orphan receptor GPR55, has also been shown to interact with THC and CBD. Because GPR55 does not have a known crystal structure, computational methods were used to create a theoretical structure using homology modeling and AlphaFold. Then using docking programs, CBD was docked into both molecules to provide a better understanding of the theoretical structures. The purpose of the second part of this study is to better understand the relationship between the endocannabinoid system and cancer, as links have been suggested in the literature. GPR55 had a total of six hotspots mutations at three different sites, based on analysis of the COSMIC database. Computational models of the R133L and R133W mutants showed potentially significant changes that may affect the overall tertiary structure.