Molecular Modeling of 1-Benzazepine Analogues that bind to the ACh Protein (2PH9) Using Hyperchem and AutoDock

Ligand interactions of the designed analogs to neuronal nicotinic Acetylcholinesterase receptor (nAChR) are being studied to see which one fit into the binding site of an ACh binding protein PDB code (2PH9).1-Benzazepine analogs improve allosteric positive modulation of the nicotinic α-7 acetylcholine receptors.The Heat of Formation, obtained using Schrödinger equations, of 8 benzazepines analogues that were designed in the Hyperchem program were calculated on the PM3 Hyperchem quantum levels.They were pre-optimized using MM + and the PM3 semi-empirical method with the Polak-Ribière conjugate gradient.The protein-ligand binding of these benzazepine analogs to ACh binding protein PDB code is being determined using the Auto Dock Tools and AutoDock Vina programs.The Affinity of the analogues under studies could be calculated using the Command Prompt of the computer, assigning specific x, y and z coordinates with a specific grid box size. It’s obtained that the ligand with the best interaction with the protein was 7-8 dimethoxy-1 BNZ-cinnamic acid with an affinity of -8.6kcal / mol and a Heat of Formation equal to -126.06 kcal / mol. These results, of the 8 ligands, were compared to Galantamine which is the commercial drug used to treat neurodegenerative diseases.