Molecular Dynamics Simulation of DENV RNA-Dependent RNA-Polymerase with Potential Inhibitor of Disulfide Cyclic Peptide

• Published in: OnLine Journal of Biological Sciences Vol. 11; no. 2; pp. 48 - 62
• Main Authors: Tambunan, Usman Sumo Friend, Noors, Raima Syahidah, Parikesit, Arli Aditya, Ronggo, Elyana, Ronggo, Wahyu
• Format: Journal Article
• Language: English
• Published: 30.09.2011
• Subjects: Dengue virus
• ISSN: 1608-4217; 1608-4217
• DOI: 10.3844/ojbsci.2011.48.62

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 leftfree to find the most suitable conformation. In actual cellular system there was a solvent which makes the enzyme to have a dynamic movement. Results: Molecular Dynamic (MD) simulation was performed to estimate more reliable condition of enzyme-ligand complex. 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 is bound to two RdRP important residues, Arg-737 and Ser-710, whereas CDGSC don'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.