Exploring Cannabidiol-TRPV3 Mediated Biological Activities-Findings From Molecular Docking, Simulation and Proteins...

Transient receptor potential vanilloid 3 (TRPV3) is a thermosensitive calcium-permeable ion channel and has a function in sensory perception, epidermal barrier function, inflammation and keratinocyte proliferation. TRPV3 dysfunction is linked with chronic pain, atopic dermatitis and neurodegenerative disorders. This study compared the binding efficacy and molecular dynamics of cannabidiol- and eugenol-TRPV3 complex(s), elucidating their ligand-protein dynamics. Computational methods, including density functional theory, molecular docking and molecular dynamics simulations, assessed electronic properties, binding affinities and interaction stability, respectively. Cannabidiol showed a higher binding affinity (-7.73 ± 0.73 kcal/mol) than eugenol (-6.0 ± 0.05 kcal/mol), driven by denser hydrophilic and hydrophobic contacts. Molecular dynamics revealed the cannabidiol-TRPV3 complex stability, with steady atomic deviation and protein compactness. Furthermore, cannabidiol-induced diverse TRPV3 conformational states, while eugenol exhibited greater flexibility. These findings highlight cannabidiol's stable, dynamic interaction with TRPV3, suggesting its potential to exert TRPV3-mediated biological effects. In contrast, eugenol may serve in transient modulation. This study offers insights into ligand-ion channel interactions, guiding drug development for TRPV3-related conditions.