In silico Screening and Molecular Interaction Studies of Tetrahydrocannabinol and its Derivatives with Acetylcholine Binding Protein

Background: Alzheimer's disease (AD) is the fourth largest cause of death among people over 65 years of age. Accumulation of β-amyloid and cholinergic deficiency are two prominent pathological descriptions for AD. Objective: Depletion of acetylcholine at the site of its action is thought to be the prime cause of AD. It has been reported that tetrahydrocannabinol (THC) exhibits anticholinesterase activity and it has been proposed as a suitable candidate for treating neurological disorders such as AD. Methods: Using an in silico approach, including virtual screening, THC and its derivatives were docked against acetylcholine binding protein (AChBP) using AutoDock. The top-ranked molecules were studied in detail using an induced fit docking approach followed by characterization of their binding affinity, toxicity and ADME properties using TOPKAT and QikProp. Results: THC_JUIT25, a novel derivative of THC, showed maximum binding affinity and was observed as a promising candidate for performing receptor-ligand interaction studies using molecular dynamics simulation. Conclusion: In this study, we propose a novel THC derivative as a potential lead molecule in the drug development strategy for treating AD.