INVESTIGATION OF THE INHIBITORY POTENTIAL OF SOME ANTIVIRAL AGENTS ON HUMAN TELOMERASE BY MOLECULAR DOCKING AND MOLECULAR DYNAMICS SIMULATION STUDIES

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dc.contributor.authorKonyar, Dilan
dc.contributor.authorMuhammed, Muhammed Tilahun
dc.date.accessioned2025-02-22T14:10:56Z
dc.date.available2025-02-22T14:10:56Z
dc.date.issued2024
dc.departmentDicle Üniversitesien_US
dc.description.abstractObjective: This study investigated the anticancer effects of nucleoside and non-nucleoside reverse transcriptase inhibitors drugs by computational methods. The study aimed to evaluate the binding capacity of these drugs on the telomerase essential N-terminal (TEN) domain of telomerase reverse transcriptase (TERT). Molecular docking was used to assess the drugs' binding potential to the TEN domain. The stability of the protein-drug combination obtained from the docking method was assessed using molecular dynamics (MD) simulation. Material and Method: The TEN domain of TERT's crystal structure was obtained from the Protein Data Bank (PDB). The crystal structure identified by the PDB code 2B2A has a resolution of 2.2 Å. The molecular docking was performed using AutoDock Vina. The complexes were visualized using Biovia Discovery Studio. The MD simulation was conducted using GROMACS 2020 as indicated. An MD simulation was conducted for 200 ns on both the complexes and the free protein. The RMSD (root mean square deviation) of the backbone protein and the molecules in relation to the backbone protein, RMSF (root mean square fluctuation), and Rg (radius of gyration) were shown via Qt Grace. Result and Discussion: Doravirine, Etravirine, Rilpivirine showed higher binding affinity to the TEN domain compared to the reference TERT inhibitor, BIBR1532, based on the docking investigation. The MD simulation analysis showed that the protein-Doravirine complex had the highest stability in remaining within the protein's binding pocket. On the contrary, the protein-Rilpivirine complex decreased stability, potentially causing the ligand to not to stay within the binding site. Doravirine was found to inhibit the TEN domain in the computational study. Therefore, the design and synthesis of novel doravirin derivatives is being considered because of the potential anticancer activity of doravirin in inhibiting the TEN domain of TERT. © 2024 University of Ankara. All rights reserved.en_US
dc.description.sponsorshipDicle Üniversitesi, (20.005); Dicle Üniversitesien_US
dc.identifier.doi10.33483/jfpau.1444259
dc.identifier.endpage585en_US
dc.identifier.issn2564-6524
dc.identifier.issue2en_US
dc.identifier.scopus2-s2.0-85196087749en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage576en_US
dc.identifier.trdizinid1236445en_US
dc.identifier.urihttps://doi.org/10.33483/jfpau.1444259
dc.identifier.urihttps://search.trdizin.gov.tr/tr/yayin/detay/1236445
dc.identifier.urihttps://hdl.handle.net/11468/29904
dc.identifier.volume48en_US
dc.indekslendigikaynakScopus
dc.indekslendigikaynakTR-Dizin
dc.language.isoenen_US
dc.publisherUniversity of Ankaraen_US
dc.relation.ispartofAnkara Universitesi Eczacilik Fakultesi Dergisien_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmzKA_Scopus_20250222
dc.subjectMD simulationen_US
dc.subjectmolecular dockingen_US
dc.subjectNNRTIen_US
dc.subjectNRTIen_US
dc.subjectTERTen_US
dc.titleINVESTIGATION OF THE INHIBITORY POTENTIAL OF SOME ANTIVIRAL AGENTS ON HUMAN TELOMERASE BY MOLECULAR DOCKING AND MOLECULAR DYNAMICS SIMULATION STUDIESen_US
dc.typeArticleen_US

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