Study of the Molecular Dynamics Stability in the Inhibitory Interaction of Tenofovir Disoproxil Fumarate against CTLA-4 in Chronic Hepatitis B Patients.
CTLA-4
Tenofovir disoproxil fumarate
hepatitis B
molecular docking
nucleotide analogue
Journal
Medical archives (Sarajevo, Bosnia and Herzegovina)
ISSN: 1986-5961
Titre abrégé: Med Arch
Pays: Bosnia and Herzegovina
ID NLM: 101635337
Informations de publication
Date de publication:
2023
2023
Historique:
received:
26
04
2023
accepted:
24
05
2023
medline:
14
9
2023
pubmed:
13
9
2023
entrez:
13
9
2023
Statut:
ppublish
Résumé
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. This study analyzed the interaction between TDF and CTLA-4 through molecular docking. 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 Autodock Vina integrated with Pyrx v.09.8. Meanwhile, the docking of proteins was accomplished 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. 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. Treatment with TDF was predicted to have inhibitory activity against CTLA-4, especially in its complex form with B7-1 and B7-2.
Sections du résumé
Background
UNASSIGNED
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
UNASSIGNED
This study analyzed the interaction between TDF and CTLA-4 through molecular docking.
Methods
UNASSIGNED
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 Autodock Vina integrated with Pyrx v.09.8. Meanwhile, the docking of proteins was accomplished 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
UNASSIGNED
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
UNASSIGNED
Treatment with TDF was predicted to have inhibitory activity against CTLA-4, especially in its complex form with B7-1 and B7-2.
Identifiants
pubmed: 37700917
doi: 10.5455/medarh.2023.77.227-230
pmc: PMC10495148
doi:
Substances chimiques
Tenofovir
99YXE507IL
CTLA-4 Antigen
0
Ligands
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
227-230Informations de copyright
© 2023 Darmadi Darmadi, Dharma Lindarto, Jelita Siregar, Tri Widyawati, Muhammad Rusda, Mustafa Mahmud Amin, Fauzi Yusuf, Putri Chairani Eyanoer, Masrul Lubis, Imelda Rey.
Déclaration de conflit d'intérêts
None declared.
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