Cannabidiol as a Promising Anti-Inflammatory Agent Targeting TYK2: Molecular Docking and Dynamic Simulation...

Area of Science:

• Biochemistry
• Computational Biology
• Pharmacology

Background:

• Multiple sclerosis (MS) is characterized by chronic inflammation linked to the JAK-STAT pathway.
• Dysregulation of this pathway highlights the need for novel therapeutic targets.

Purpose of the Study:

• To investigate the interaction between natural cannabinoids, specifically cannabidiol (CBD), and TYK2.
• To utilize computational in silico methods for evaluating this potential interaction.

Main Methods:

• Employed a combined molecular docking and molecular dynamics (MD) simulation workflow.
• Utilized MOE for docking and GROMACS for 20 ns MD simulations under NVT and NPT conditions.
• Analyzed complex stability and ligand-protein interactions.

Main Results:

• CBD exhibited a competitive docking score (-7.31 kcal/mol) and stable complex formation with TYK2.
• MD simulations indicated lower RMSD fluctuations for CBD-TYK2 compared to deucravacitinib.
• Analysis revealed preserved protein compactness and a binding mode dominated by hydrophobic interactions.

Conclusions:

• CBD demonstrates a stable interaction with TYK2 via a unique binding mode, distinct from deucravacitinib.
• The structural integrity of TYK2 was maintained during simulations.
• CBD shows promise as a potential therapeutic candidate for MS-related inflammation, warranting further investigation.