Molecular Dynamics Simulation of Bioactive Compounds Against Six Protein Target of Sars-Cov-2 As Covid-19 Antivirus Candidates

Fikry Awaluddin, Irmanida Batubara, Setyanto Tri Wahyudi


Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus that causes Coronavirus 2019 (COVID-19). To date, there has been no proven effective drug for the treatment or prevention of COVID-19. A study on developing inhibitors for this virus was performed using molecular dynamics simulation. 3CL-Pro, PL-Pro, Helicase, N, E, and M protein were used as protein targets. This study aimed to determine the stability of the selected protein-ligand complex through molecular dynamics simulation by Amber20 to propose bioactive compounds from natural products that have potential as a drug for COVID-19. Based on our previous study, the best value of free binding energy and protein-ligand interactions of the candidate compounds are obtained for each target protein through molecular docking. Corilagin (-14.42 kcal/mol), Scutellarein 7-rutinoside (-13.2 kcal/mol), Genistein 7-O-glucuronide (-10.52 kcal/mol), Biflavonoid-flavone base + 3O (-11.88 and -9.61 kcal/mol), and Enoxolone (-6.96 kcal/mol) has the best free energy value at each protein target. In molecular dynamics simulation, the 3CL-Pro-Corilagin complex was the most stable compared to other complexes, so that it was the most recommended compound. Further research is needed to test the selected ligand activity, which has the lowest free energy value of the six target proteins.


Bioactive Compound, COVID-19, Molecular Dynamic, SARS-CoV-2


Anandakrishnan, R., Aguilar, B., & Onufriev, A. V. (2012). H++ 3.0: automating pK prediction and the preparation of biomolecular structures for atomistic molecular modeling and simulations. Nucleic Acids Research, 40(Web Server issue), W537–W541.

Case, D.A., Aktulga, H.M., Belfon, K., Ben-Shalom, I.Y., Brozell, S.R., Cerutti, D.S., T.E. Cheatham, III., Cisneros, G.A., Cruzeiro, V.W.D., Darden, T.A., Duke, R.E., Giambasu, G., Gilson, M.K., Gohlke, H., Goetz, A.W., Harris, R., Izadi, S., Izmailov, S, P. A. (2021). Amber 2021. In University of California, San Francisco. Retrieved from

Dhanik, A., McMurray, J. S., & Kavraki, L. E. (2012). Binding modes of peptidomimetics designed to inhibit STAT3. PloS One, 7(12), e51603.

Gao, Y., Mei, Y., & Zhang, J. Z. H. (2015). Treatment of Hydrogen Bonds in Protein Simulations. In Advanced Materials for Renewable Hydrogen Production, Storage and Utilization (Vol. 32, pp. 1854–1858). InTech.

Genheden, S., & Ryde, U. (2015). The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities. Expert Opinion on Drug Discovery, 10(5), 449–461.

Gogoi, B., Chowdhury, P., Goswami, N., Gogoi, N., Naiya, T., Chetia, P., Mahanta, S., Chetia, D., Tanti, B., Borah, P., Handique, P. J. (2021). Identification of potential plant-based inhibitor against viral proteases of SARS-CoV-2 through molecular docking, MM-PBSA binding energy calculations and molecular dynamics simulation. Molecular Diversity, 25(3), 1963–1977.

Gordon, J. C., Myers, J. B., Folta, T., Shoja, V., Heath, L. S., & Onufriev, A. (2005). H++: a server for estimating pKas and adding missing hydrogens to macromolecules. Nucleic Acids Research, 33(Web Server issue), W368-71.

Humphrey, W., Dalke, A., & Schulten, K. (1996). VMD: Visual molecular dynamics. Journal of Molecular Graphics, 14(1), 33–38.

Kapoor, R., Sharma, B., & Kanwar, S. S. (2017). Antiviral Phytochemicals: An Overview. Biochemistry & Physiology: Open Access, 06(02).

Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., He, S., Li, Q., Shoemaker, B. A., Thiessen, P. A., Yu, B., Zaslavsky, L., Zhang, J., Bolton, E. E. (2019). PubChem 2019 update: improved access to chemical data. Nucleic Acids Research, 47(D1), D1102–D1109.

Kuzmanic, A., & Zagrovic, B. (2010). Determination of ensemble-average pairwise root mean-square deviation from experimental B-factors. Biophysical Journal, 98(5), 861–871.

Madej, B. D., & Walker, R. (2020). AMBER Tutorial B0 - An Introduction to Molecular Dynamics Simulations using AMBER. Retrieved from

Martínez, L. (2015). Automatic identification of mobile and rigid substructures in molecular dynamics simulations and fractional structural fluctuation analysis. PLoS ONE, 10(3), 1–10.

Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., & Olson, A. J. (2009). AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry, 30(16), 2785–2791.

Myers, J., Grothaus, G., Narayanan, S., & Onufriev, A. (2006). A simple clustering algorithm can be accurate enough for use in calculations of pKs in macromolecules. Proteins: Structure, Function, and Bioinformatics, 63(4), 928–938.

Roe, D. R., & Cheatham, T. E. (2013). PTRAJ and CPPTRAJ: Software for Processing and Analysis of Molecular Dynamics Trajectory Data. Journal of Chemical Theory and Computation, 9(7), 3084–3095.

Tan, Y. J., Lim, S. G., & Hong, W. (2005). Characterization of viral proteins encoded by the SARS-coronavirus genome. Antiviral Research, 65(2), 69–78.

Yoshimoto, F. K. (2020). The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2 or n-COV19), the Cause of COVID-19. Protein Journal, 39(3), 198–216.

Zhang, C., Zheng, W., Huang, X., Bell, E. W., Zhou, X., & Zhang, Y. (2020). Protein Structure and Sequence Reanalysis of 2019-nCoV Genome Refutes Snakes as Its Intermediate Host and the Unique Similarity between Its Spike Protein Insertions and HIV-1. Journal of Proteome Research, 19(4), 1351–1360.

Zikri, A. T., Pranowo, H. D., & Haryadi, W. (2020). Stability, Hydrogen Bond Occupancy Analysis and Binding Free Energy Calculation from Flavonol Docked in DAPK1 Active Site Using Molecular Dynamic Simulation Approaches. Indonesian Journal of Chemistry, 21(2), 383.

Full Text: PDF

DOI: 10.15408/jkv.v7i2.21634


  • There are currently no refbacks.

Copyright (c) 2021 Irmanida Batubara, Setyanto Tri Wahyudi, Fikry Awaluddin

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.