Cannabis Compounds: Docking and Dynamics Study

Cannabis molecules exhibit significant therapeutic potential, offering promising prospects in healthcare. This in silico study aims to evaluate the affinity and stability of non-psychotropic cannabis-derived compounds (CBC, CBD, CBG, CBN, and β-Cannabispiranol) with CB1 and CB2 receptors to identify the ligand with the highest interaction potential. Using MOE (Molecular Operating Environment) for molecular docking and GROMACS for molecular dynamics simulations, the interactions between these ligands and their targets were analyzed. Results reveal that cannabis compounds interact favorably with both CB1 and CB2 receptors, with a clear preference for CB2. CBG demonstrated the highest affinity with CB2 (-7.9008 kcal/mol), forming two key bonds: an H-arene bond and a hydrogen bond with phenylalanine 183. The CB2-CBG complex exhibited remarkable stability over 8000 ps, with an RMSD of 0.6993 Å. CBD showed the best affinity with CB1 (-7.4857 kcal/mol), forming a hydrogen bond with methionine 363 and an RMSD of 1.6918 Å, also within acceptable limits. In conclusion, CBG emerges as the most promising ligand due to its stable, reversible interaction and high affinity potential with CB2.