Title:In silico Screening and Molecular Interaction Studies of Tetrahydrocannabinol and its Derivatives with Acetylcholine Binding Protein
Volume: 12
Issue: 2
Author(s): Priya P. Panigrahi, Ramit Singla, Ankush Bansal, Moacyr Comar Junior, Vikas Jaitak, Ragothaman M. Yennamalli and Tiratha Raj Singh*
Affiliation:
- Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan- 173234 (HP),India
Keywords:
Acetylcholine binding protein, alzheimer’s disease, tetrahydrocannabinol, molecular docking,
molecular dynamics, dronabinol.
Abstract: 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.
