Molecular Dynamics Study of Thymoquinone and Madecassoside as Potential Anti-Parkinson’s Agents via Dopamine D2 Receptor Modulation
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Abstract
Parkinson's disease is a neurodegenerative disease characterized by degeneration of dopaminergic neurons. There is no drug can inhibit its progression. The dopamine receptor D2 (DRD2) subtype is pivotal in Parkinson's disease for decreasing locomotor activity. Thymoquinone is an active component of N. sativa that prevents dopamine degradation. Madecassoside is a major chemical component of C.asiatica that contributes to anti-apoptosis in Parkinson's disease. There is currently no research on the two chemicals working together as an anti-Parkinsonian. This study investigated the potential of thymoquinone and madecassoside in regulating the dopamine DRD2 through an in silico approach. The PubChem database was used to retrieve SMILES for each bioactive chemical. The 3D structure of the target protein was obtained from the RSCB PDB database, while that of the PDB ligand control rotigotine (CID: 59227) and the wet-lab control pramipexole (CID: 119570) were obtained from the PubChem database. Molecular dynamics simulations were conducted with Biosciences. The results showed the compounds had a high binding affinity potential, particularly when compared to the wet-lab control, pramipexole. The overlay visualization findings were consistent with the results of H-bond, SASA, and RMSD, indicating that the control drug ligand rotigotine and thymoquinone could better preserve the conformational stability of the DRD2 protein than other ligands. Thymoquinone, a bioactive chemical, acted as the most similar activator to rotigotine. The madecassoside formed the greatest protein-ligand hydrogen bonds. Thymoquinone showed promise as a DRD2 modulator with neuroprotective potential, while madecassoside requires optimization. Findings support natural compounds for Parkinson’s disease via DRD2 modulation.
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