THC and Endocannabinoid interactions with Oleic acid-CB1r active site via Molecular Dynamics

Abstract

Oleic acid, THC, Anandamide and 2-arachidonoylglycerol (2-AG) were computer modelled and simulated to interact with amino acids located within the endocannabinoid receptor CB1R’s binding site for oleic acid. Models were created using Avogadro molecule editor and the CB1R binding site sequence was determined using Bio3D and the 5TGZ.pdb file from the RCSB Protein Data Bank website. A new molecule was devised from the structure and electrostatic potential map of THC and was also simulated to interact with the oleic acid binding site amino acids. The simulated ligand-binding site complexes were optimized using different molecular force fields and the energy of each ligand-binding site complex, once optimized, was recorded. The oleic acid complex was found to have the lowest average energy state of 583.422 Kj/mol, followed by anandamide (681.874 Kj/mol), 2-AG (740.268 Kj/mol), THC (808.356 Kj/mol), and the edited THC molecule (857.793 Kj/mol).