Molecular Docking and Dynamics Simulation Analysis of Thymoquinone and Thymol Compounds from Nigella sativa L. that Inhibits P38 Protein: Probable Remedies for Hepatocellular Carcinoma.
BACKGROUND
Currently, a novel antagonist against p38 is being designed and applied to inhibit hepatocellular carcinoma. Protein-ligand interaction plays a major role in the identification of the possible mechanism for the pharmacological action. The involvement of p38 remains an important target for anticancer drug development as its activation induces apoptosis in hepatoma cells.


OBJECTIVE
The aim is to identify the best candidate from the plants of N. sativa which binds with the hepatocellular carcinoma (HCC) targets by computational approach.


MATERIALS AND METHODS
The reported phytoconstituents such as thymoquinone and thymol present in the plant, N. sativa were docked with the HCC target such as p38. Structures of phytoconstituents were prepared using ChemDraw Ultra 10 software and converted into its 3D PDB structure and minimized using Discovery Studio client 2.5. The target protein, p38 was retrieved from RCSB PDB. Lipinski's rule and ADMET toxicity profiling were carried out on the phytoconstituents of the N. sativa, and the compounds were further promoted for molecular docking and MD simulation analysis.


RESULTS
The docking results revealed promising inhibitory potential of thymoquinone against p38 with binding energy of -7.67 kcal/mole as compared to its known standard doxorubicin having binding energy of -6.68 kcal/mol respectively. Further, molecular dynamic (MD) simulations for 5ns were conducted for optimization, flexibility prediction, and determination of folded p38 stability. The p38-thymoquinone complex was found to be quite stable with RMSD value of 0.2 nm.


CONCLUSION
Obtained results propose thymoquinone binding energy on the selected targets. Hence, this compound bears outstanding potential against hepatocellular carcinoma and has to be taken up for experimental work against hepatocellular carcinoma.
['Tabassum|Heena|H|', 'Ahmad|Iffat Z|IZ|']
D000970:Antineoplastic Agents D016227:Benzoquinones D020134:Catalytic Domain D004317:Doxorubicin D004353:Drug Evaluation, Preclinical D006801:Humans D062105:Molecular Docking Simulation D056004:Molecular Dynamics Simulation D011485:Protein Binding D013943:Thymol D048051:p38 Mitogen-Activated Protein Kinases
molecular docking Nigella sativa hepatocellular carcinoma phytoconstituents Antioxidant simulation.