PENAMBATAN DAN SIMULASI DINAMIKA MOLEKULER SENYAWA BIOAKTIF TANAMAN BAWANG DAYAK (Eleutherine Sp.) SEBAGAI INHIBITOR KAPSID VIRUS HEPATITIS B
Keywords:
bawang dayak, kapsid virus hepatitis B, penambatan molekul, simulasi dinamika molekuler
Abstract
Hepatitis B merupakan penyakit infeksi hati yang disebabkan oleh virus hepatitis B. Kapsid pada virus hepatitis B adalah lapisan yang berfungsi untuk melindungi RNA dan DNA virus dari kerusakan. Tanaman yang diketahui memiliki aktivitas sebagai antivirus adalah bawang dayak. Penelitian ini bertujuan untuk menghasilkan senyawa hit hasil penambatan dan simulasi dinamika molekuler. Target Makromolekul yang digunakan adalah PDB ID : 5GMZ dan 33 senyawa dari tanaman bawang dayak. Penambatan molekuler menggunakan AutoDock Vina dan validasinya dengan menentukan kurva ROC dan perhitungan nilai AUC, menentukan RMSD secara redocking. Seleksi dengan aturan Lipinski Rule of 5 untuk menghasilkan senyawa yang dapat digunakan secara oral. Simulasi dinamika molekuler menggunakan program Gromacs 5.1.5 dan g_mmpbsa. Hasil seleksi Lipinski Rule of 5 menghasilkan 28 senyawa. Hasil penambatan menunjukkan senyawa Eleuthosida A memiliki nilai afinitas lebih negatif (-7,5 kkal/mol) dibandingkan pembanding 6XU dan isothiafludine (-7,4 dan -6,1 kkal/mol). Simulasi dinamika selama 20ns menunjukkan nilai RMSD dan RMSF Eleuthosida A dalam keadaan stabil dengan okupansi ikatan hidrogen sebesar 18,81% pada asam amino Asp29. Energi bebas MM-PBSA pada senyawa Eleuthosida A merupakan senyawa dengan paling negatif yaitu -133,430 kkal/mol. Berdasarkan hasil tersebut, Eleuthosida A dapat dijadikan kandidat inhibitor kapsid virus hepatitis B.
References
Daftar Pustaka
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[23] Kumari, R., Kumar, R., & Lynn, A. (2014). G-mmpbsa -A GROMACS tool for high-throughput MM-PBSA calculations. Journal of Chemical Information and Modeling, 54(7), 1951–1962. d
[1] World Health Organization. (2021). Hepatitis B. Geneva: World Health Organization.
[2] Badan Penelitian dan Pengembangan Kesehatan. (2018). Laporan Nasional RKD 2018 (p. 198). Indonesia: Badan Penelitian dan Pengembangan Kesehatan.
[3] Firdayani, ., Kusumaningrum, S., & Miranti, Y. R. (2017). Potensi Senyawa Bioaktif Tanaman Genus Phyllanthus Sebagai Inhibitor Replikasi Virus Hepatitis B. Jurnal Bioteknologi & Biosains Indonesia (JBBI), 4(2), 85. doi: 10.29122/jbbi.v4i2.2589
[4] Lubis, I. A. (2021). Eleutherine bulbosa (Mill.) Urb). 9(2), 85–92.
[5] Prayitno, B., Mukti, B. H., & Lagiono. (2018). Optimasi potensi bawang dayak (Eleutherine sp.) sebagai bahan obat alternatif. Jurnal Pendidikan Hayati, 4(3), 149–158. Retrieved from https://jurnal.stkipbjm.ac.id/index.php/JPH/article/view/436
[6] Insanu, M., Kusmardiyani, S., & Hartati, R. (2014). Recent Studies on Phytochemicals and Pharmacological Effects of Eleutherine Americana Merr. Procedia Chemistry, 13, 221–228. doi: 10.1016/j.proche.2014.12.032
[7] Qiu, Z., Lin, X., Zhou, M., Liu, Y., Zhu, W., Chen, W., Zhang, W., Guo, L., Liu, H., Wu, G., Huang, M., Jiang, M., Xu, Z., Zhou, Z., Qin, N., Ren, S., Qiu, H., Zhong, S., Zhang, Y., … Tang, G. (2016). Design and synthesis of orally bioavailable 4-methyl heteroaryldihydropyrimidine based hepatitis B virus (HBV) capsid inhibitors. Journal of Medicinal Chemistry, 59(16), 7651–7666. doi: 10.1021/ACS.JMEDCHEM.6B00879
[8] Wardaniati, I., & Azhari Herli, M. (2018). Studi Molecular Docking Senyawa Golongan Flavonol Sebagai Antibakteri. JOPS (Journal Of Pharmacy and Science), 1(2), 20–27. doi: 10.36341/jops.v1i2.489
[9] Arba, M. (2019). Buku Ajar Farmasi Komputasi. Yogyakarta: Deepublish.
[10] Kelutur, F. J., Mustarichie, R., & Umar, A. K. (2020). Virtual Screening Kandungan Senyawa Kipas Laut (Gorgonia mariae) sebagai Anti-Asma. ALCHEMY Jurnal Penelitian Kimia, 16(2), 48. doi: 10.20961/alchemy.16.2.39965.48-59
[11] Chen, X., Li, H., Tian, L., Li, Q., Luo, J., & Zhang, Y. (2020). Analysis of the Physicochemical Properties of Acaricides Based on Lipinski’s Rule of Five. Journal of Computational Biology, 27(9), 1397–1406. doi: 10.1089/cmb.2019.0323
[12] Jagiello, K., Sosnowska, A., Kar, S., & Demkowicz, S. (2017). Geometry optimization of steroid sulfatase inhibitors - the influence on the free binding energy with STS. doi: 10.1007/s11224-016-0903-x
[13] Opo, F. A. D. M., Rahman, M. M., Ahammad, F., Ahmed, I., Bhuiyan, M. A., & Asiri, A. M. (2021). Structure based pharmacophore modeling, virtual screening, molecular docking and ADMET approaches for identification of natural anti-cancer agents targeting XIAP protein. Scientific Reports, 11(1), 1–18. doi: 10.1038/s41598-021-83626-x
[14] Sangande, F., Julianti, E., & Tjahjono, D. H. (2020). Ligand-based pharmacophore modeling, molecular docking, and molecular dynamic studies of dual tyrosine kinase inhibitor of egfr and vegfr2. International Journal of Molecular Sciences, 21(20), 1–16. doi: 10.3390/ijms21207779
[15] Maisaroh, & Purwanto, W. (2019). Tinjauan Termodinamika dan Kesetimbangan Kimia dalam Hubungan Perubahan Suhu Terhadap Konversi Reaksi Epoksidasi Asam Oleat Berbasis Sawit. Prosiding Seminar Nasional Pengabdian Masyarakat, September 2019, 1–11. Retrieved from https://jurnal.umj.ac.id/index.php/semnaskat/article/view/5381/3594
[16] Sharmila, C. M., Devi, R. C., Sureka, A., MuthuKumar, N. J., & Banumathi, V. (2019). In silico analysis of the effect of vasicine and vasinone against human tyrosinase receptor in the management of hyperpigmentation of skin diseases. Asian Journal of Pharmacy and Pharmacology, 5(3), 518–524. doi: 10.31024/ajpp.2019.5.3.13
[17] Bernaldez, M. J. A., Billones, J. B., & Magpantay, A. (2018). In silico analysis of binding interactions between GSK983 and human DHODH through docking and molecular dynamics. AIP Conference Proceedings, 2045(December). doi: 10.1063/1.5080886
[18] Dermawan, D., Sumirtanurdin, R., & Dewantisari, D. (2019). Molecular Dynamics Simulation Estrogen Receptor Alpha againts Andrographolide as Anti Breast Cancer. Indonesian Journal of Pharmaceutical Science and Technology, 6(2), 65. doi: 10.24198/ijpst.v6i2.18168
[19] Sari, B. L., Ibrahim, S., & Tjahjono, D. H. (2021). Pharmacophore Modeling, Docking, and Molecular Dynamics Simulation of Flavonoids as Inhibitors of Urokinase-type Plasminogen Activator. Journal of Mathematical and Fundamental Sciences, 53(3), 451–465. doi: 10.5614/J.MATH.FUND.SCI.2021.53.3.8
[20] Abdurrahman, F., Tahir, I., Pradipta, M. F., Kimia, D., Gadjah, U., & Sleman, K. (2018). Desain sintesis polimer tercetak molekular brazilein dengan simulasi dinamika molekular. Prosiding Seminar Nasional Kimia Dan Pembelajarannya (SNKP) 2018, November, 182–189.
[21] Rafi, M. O., Bhattacharje, G., Al-Khafaji, K., Taskin-Tok, T., Alfasane, M. A., Das, A. K., Parvez, M. A. K., & Rahman, M. S. (2020). Combination of QSAR, molecular docking, molecular dynamic simulation and MM-PBSA: analogues of lopinavir and favipiravir as potential drug candidates against COVID-19. Journal of Biomolecular Structure and Dynamics, 0(0), 1–20. doi: 10.1080/07391102.2020.1850355
[22] Wang, E., Sun, H., Wang, J., Wang, Z., Liu, H., Zhang, J. Z. H., & Hou, T. (2019). End-Point Binding Free Energy Calculation with MM/PBSA and MM/GBSA: Strategies and Applications in Drug Design [Review-article]. Chemical Reviews, 119(16), 9478–9508. doi: 10.1021/acs.chemrev.9b00055
[23] Kumari, R., Kumar, R., & Lynn, A. (2014). G-mmpbsa -A GROMACS tool for high-throughput MM-PBSA calculations. Journal of Chemical Information and Modeling, 54(7), 1951–1962. d
Published
2023-12-01
How to Cite
Lohita Sari, B., Suhendar, U., & Hamdani, R. (2023). PENAMBATAN DAN SIMULASI DINAMIKA MOLEKULER SENYAWA BIOAKTIF TANAMAN BAWANG DAYAK (Eleutherine Sp.) SEBAGAI INHIBITOR KAPSID VIRUS HEPATITIS B. Jurnal Farmamedika (Pharmamedika Journal), 8(2), 103-110. https://doi.org/10.47219/ath.v8i2.201
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