VALIDASI INTERNAL KOMPLEKS RESEPTOR HMG-COA REDUKTASE (PDB:1HWK)-ATORVASTATIN SEBAGAI ANTIKOLESTEROL DENGAN METODE PENAMBATAN ULANG

Gerry Nugraha, Suprayetno Suprayetno, Dimas Raka Pangestu

Abstract


Latar Belakang: Penyakit hiperlipidemia cenderung terjadi pada kelompok usia produktif dari umur 25 tahun keatas, tanpa pengobatan yang tepat dapat menyebabkan timbulnya penyakit penyumbatan pembuluh darah, berubah menjadi penyakit stroke, jantung koroner, dan penyakit berbahaya lainnya. Atorvastatin merupakan obat yang mengurangi resiko penyakit kardiovaskular, dengan menghambat produksi kolesterol endogen dalam hati. Kimia komputasi mampu memberikan informasi interaksi antara atorvastatin dengan reseptornya, salah satunya berupa validasi internal melalui penambatan ulang. Tujuan: Melakukan validasi berupa penambatan ulang ligan atorvastatin terhadap reseptor HMG-CoA reduktase (kode pdb: 1HWK). Metode: Metode yang digunakan berupa uji in silico melalui penambatan ulang ligan terhadap reseptor sebanyak 1000 kali, model yang digunakan adalah hasil dari simulasi dinamika molekul snapshot nomor 87. Hasil: Validasi internal dengan penambatan ulang ligan atorvastatin sebanyak 1,000 kali menghasilkan nilai Root Mean Square Deviation (RMSD) sebesar 0,3181Å. Kesimpulan: Data RMSD menunjukan atorvastatin bersifat stabil dalam kantung ikatan reseptor, sistem yang dihasilkan bersifat reprodusibel dan dapat digunakan untuk keperluan penelitian selanjutnya berupa validasi retrospektif

 

Kata Kunci: Penambatan Ulang, Atorvastatin, HMG-CoA Reduktase, Kimia Komputasi


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References


Istyastono, E., & Gani, M. (2021). Identification of Interactions of ABT-341 to Dipeptidyl Peptidase IV during Molecular Dynamics Simulations. Jurnal Farmasi Galenika (Galenika Journal of Pharmacy) (e-Journal), 7(2), 91–98.

Lawal, H. A., Uzairu, A., & Uba, S. (2020). QSAR, molecular docking, design, and pharmacokinetic analysis of 2-(4-fluorophenyl) imidazol-5-ones as anti-breast cancer drug compounds against MCF-7 cell line. Journal of Bioenergetics and Biomembranes, 52(6), 475–494.

Marcou, G., & Rognan, D. (2007). Optimizing fragment and scaffold docking by use of molecular interaction fingerprints. Journal of Chemical Information and Modeling, 47(1), 195–207.

Nelson, R. H. (2013). Hyperlipidemia as a Risk Factor for Cardiovascular Disease. Primary Care - Clinics in Office Practice, 40(1), 195–211.

Nugraha, G., & Istyastono, E. P. (2020). Pembuatan Protokol Penapisan Virtual Berbasis Stuktur ( pvbs ) untuk Identifikasi Ligan Inhibitor Reseptor Platelet-Activating Factor ( PAF-r ) sebagai Target Terapeutik Asma menggunakan YASARA. 2016(Tabel 1), 35–42.

Nugraha, G., Pranowo, H. D., Mudasir, M., & Istyastono, E. P. (2022). Virtual Target Construction for Discovery of Human Histamine H4 Receptor Ligands Employing a Structure-Based Virtual Screening Approach. International Journal of Applied Pharmaceutics, 14(4), 213–218.

Istyastono, E., & Gani, M. (2021). Identification of Interactions of ABT-341 to Dipeptidyl Peptidase IV during Molecular Dynamics Simulations. Jurnal Farmasi Galenika (Galenika Journal of Pharmacy) (e-Journal), 7(2), 91–98.

Lawal, H. A., Uzairu, A., & Uba, S. (2020). QSAR, molecular docking, design, and pharmacokinetic analysis of 2-(4-fluorophenyl) imidazol-5-ones as anti-breast cancer drug compounds against MCF-7 cell line. Journal of Bioenergetics and Biomembranes, 52(6), 475–494.

Marcou, G., & Rognan, D. (2007). Optimizing fragment and scaffold docking by use of molecular interaction fingerprints. Journal of Chemical Information and Modeling, 47(1), 195–207.

Nelson, R. H. (2013). Hyperlipidemia as a Risk Factor for Cardiovascular Disease. Primary Care - Clinics in Office Practice, 40(1), 195–211.

Nugraha, G., & Istyastono, E. P. (2020). Pembuatan Protokol Penapisan Virtual Berbasis Stuktur ( pvbs ) untuk Identifikasi Ligan Inhibitor Reseptor Platelet-Activating Factor ( PAF-r ) sebagai Target Terapeutik Asma menggunakan YASARA. 2016(Tabel 1), 35–42.

Nugraha, G., Pranowo, H. D., Mudasir, M., & Istyastono, E. P. (2022). Virtual Target Construction for Discovery of Human Histamine H4 Receptor Ligands Employing a Structure-Based Virtual Screening Approach. International Journal of Applied Pharmaceutics, 14(4), 213–218.

Purnamasari, R., Manggau, M. A., & Amran, M. Y. (2018). Hubungan Antara Penggunaan Obat Atorvastatin Terhadap Perbaikan Klinis Pasien Stroke Iskemik Di Rsup Dr. Wahidin Sudirohusodo. Majalah Farmasi Dan Farmakologi, 22(1), 8–12.

Rosada, A., Kassner, U., Weidemann, F., König, M., Buchmann, N., Steinhagen-Thiessen, E., & Spira, D. (2020). Hyperlipidemias in elderly patients: Results from the Berlin Aging Study II (BASEII), a cross-sectional study. Lipids in Health and Disease, 19(1), 1–10.

Sakai, K.,et all. (2018). Myeloid hmg-coa (3-hydroxy-3-methylglutaryl-coenzyme a) reductase determines atherosclerosis by modulating migration of macrophages. Arteriosclerosis, Thrombosis, and Vascular Biology, 38(11), 2590–2600.

Setiawati, A., Riswanto, F. D. O., Yuliani, S. H., & Istyastono, E. P. (2014). Retrospective validation of a structure-based virtual screening protocol to identify ligands for estrogen receptor alpha and its application to identify the alpha-mangostin binding pose. Indonesian Journal of Chemistry, 14(2), 103–108.

Shitara, Y., & Sugiyama, Y. (2006). Pharmacokinetic and pharmacodynamic alterations of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors: Drug-drug interactions and interindividual differences in transporter and metabolic enzyme functions. Pharmacology and Therapeutics, 112(1), 71–105.

Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455–461.

Uchikoga, N., Matsuzaki, Y., Ohue, M., Hirokawa, T., & Akiyama, Y. (2013). Re-Docking Scheme for Generating Near-Native Protein Complexes by Assembling Residue Interaction Fingerprints. PLoS ONE, 8(7).

World Health Organization. (2018). NCDs Country Profiles 2018 WHO. 224.




DOI: https://doi.org/10.36729/bi.v14i2.963

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