Molecular Dynamics, Simulation of Protein-Protein Complex and their Role in Cytoprotective Process in Ethanol-induced Toxicity of HepG2 Cell Line

Aim: To examine the protein-protein interaction of Wolbachia Surface Protein (WSP of Uzifly) with six proteins involved in Ethanol-induced toxicity and the proteins involved in its cytoprotective process in HepG2 cell line (CYP2E1, Superoxide dismutase, Catalase, Death-associated protein kinase1, Alcohol dehydrogenases (Alpha/beta/gamma) and Cytochrome-C) and to study real time molecular dynamics.

Methodology: Modelled structure of WSP of Uzifly was retrieved from our laboratory archive. The proteins involved in the Ethanol-induced toxicity and the proteins involved in its cytoprotective process in HepG2 cell line were chosen based on the literature study. The six proteins like CYP2E1, Superoxide dismutase, Catalase, Death-associated protein kinase1, Alcohol dehydrogenases (Alpha/beta/gamma) and Cytochrome-C which are involved in the Ethanol-induced toxicity and the proteins involved in its cytoprotective process in HepG2 cell line were retrieved from PDB database with ID: PDB (3T3Z), PDB (2C9V), PDB (1DGG), PDB (2YAK), PDB (1U3W) and PDB (3NWV) respectively. Docking study was processed using ZDOCK and the best poses of protein were sorted using rDock. Finally, the atomic level interaction was studied for the best-scored protein-protein complex. The best complex was further subjected to molecular dynamics simulation to study its stability using standard dynamics cascade tool.

Results: From the results, it was observed that three proteins such as Cytochrome-C, CYP2E1 and Superoxide dismutase have more favourable shape complementarity for WSP binding to exhibit the cytoprotective process. However, the interaction analysis was done only for the top complex, Cytochrome-C-WSP. Time dependent parameter analysis of best complex Cytochrome-C-WSP showed that root-mean-square deviation (RMSD) values initially deviated but it was stabilized at the end of 1ns dynamics. The radius of gyration (Rg) during dynamics was within the limit.

Conclusion: This insilico study revealed that WSP has cytoprotective potential and therapeutical application.