Darmadi Darmadi, Dharma Lindarto, Jelita Siregar, Tri Widyawati, Muhammad Rusda, Mustafa Mahmud Amin, Fauzi Yusuf, Putri Chairani Eyanoer, Masrul Lubis, Imelda Rey
Background: Tenofovir disoproxil fumarate (TDF) is a first-line nucleotide analog (NA) drug for hepatitis B therapy. Long-term NA therapy increases peripheral T cell levels to enhance antiviral response, while CTLA-4 inhibits the activation. Objective: This study analyzed the interaction between TDF and CTLA-4 through molecular docking. Methods: Target protein and ligand data mining were performed, and proteins were prepared by removing water molecules in the Discovery Studio 2019 software. The energy minimization was performed on ligands using Pyrx v.0.9.8 software. Protein-ligand docking was performed using Aut-odock Vina integrated with Pyrx v.09.8. Meanwhile, the docking of proteins was accom-plished using the Haddock server. The BioVia Discovery Studio 2019 software visualized the interaction between the compound and the docked protein. Molecular dynamics simulations were carried out using the YASARA Dynamic program developed by Biosciences GmbH. Results: TDF ligand has good and stable inhibitory activity against the CTLA-4/ B7-1 and CTLA4/B7-2 complexes. TDF docking has been shown to initiate conformational changes, indicating the ligand’s inhibitory activity. The significant conformational changes based on superimposition results were shown by the CTLA-4/TDF/B7-2 and CTLA-4/B7-1/ TDF complexes. TDF in all ligands undergoes bonding and displacement of binding sites. Conclusion: Treatment with TDF was predicted to have inhibitory activity against CTLA-4, especially in its complex form with B7-1 and B7-2. © 2023 Darmadi Darmadi, Dharma Lindarto, Jelita Siregar, Tri Widyawati, Muhammad Rusda, Mustafa Mahmud Amin, Fauzi Yusuf, Putri Chairani Eyanoer, Masrul Lubis, Imelda Rey.
Philosophy Doctor in Medicine Program, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia; Department of Internal Medicine, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia; Department of Clinical Pathology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia; Department of Pharmacology and Therapeutic, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia; Master Program in Tropical Medicine, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia; Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia; Department of Psychiatry, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia; Department of Internal Medicine, Faculty of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia; Department of Public Health, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
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