Molecular dynamics simulation of denv RNA-dependent RNA-polymerase with potential inhibitor of disulfide cyclic peptide

Abstract

Problem statement: Our researches have proposed two ligands of disulfide cyclic polypeptide, which are CDEEC and CDGSC as potential inhibitor of DENV RNA-dependent RNApolymerase by molecular docking. Approach: Methodological approach was conducted to determine the best ligand to act as inhibitor. Molecular docking simulation was conducted without a solvent in which enzyme was made rigid and ligand was left free to find the most suitable conformation. In actual cellular system there is a solvent which makes the enzyme to have a dynamic movement. Results: Therefore in this study, Molecular Dynamic (MD) simulation was performed to estimate more reliable condition of enzyme-ligand complex. In this study, molecular dynamics simulation was performed during 5 ns with two different temperatures, 300 and 312 K. At the end of MD simulation at 300 K, CDEEC bound to two RdRp important residues, Arg-729 and Arg-737 while CDGSC didn’t bind to any important residues. Conclusion: Simulation at 312 K also showed almost similar result. CDEEC was bound to two RdRP important residues, Arg-737 and Ser-710, whereas CDGSC didn’t bind to any important residues. Based on the result of these two simulations, CDEEC is proposed as a better inhibitor of RdRp dengue virus and feasible to be developed as anti-dengue drug.