Computational design of a full-length model of HIV-1 integrase: modeling of new inhibitors and comparison of their calculated binding energies with those previously studied

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dc.contributor.authorErcan, Selami
dc.contributor.authorPirinccioglu, Necmettin
dc.date.accessioned2024-04-24T16:01:59Z
dc.date.available2024-04-24T16:01:59Z
dc.date.issued2013
dc.departmentDicle Üniversitesien_US
dc.description.abstractA full-length model of integrase (IN) of the human immunodeficiency virus type 1 (HIV-1) was constructed based on the distinctly resolved X-ray crystal structures of its three domains, named N-terminal, catalytic core and C-terminal. Thirty-one already known inhibitors with varieties of structural differences as well as nine newly tested ones were docked into the catalytic core. The molecular dynamic (MD) and binding properties of these complexes were obtained by MD calculations. The binding energies calculated by molecular mechanic/Poisson Boltzmann solvation area were significantly correlationed with available IC50. Four inhibitors including two newly designed were also docked into the full-length model and their MD behaviors and binding properties were calculated. It was found that one of the newly designed compounds forms a better complex with HIV-1 IN compared to the rest including raltegravir. MD calculations were performed with AMBER suite of programs using ff99SB force field for the proteins and the general Amber force field for the ligands. In conclusion, the results have produced a promising standpoint not only in the construction of the full-length model but also in development of new drugs against it. However, the role of multimer formation and the involvement of DNAs, and their subsequent effect on the complexation and inhibition, are required to arrive at a conclusive decision.en_US
dc.identifier.doi10.1007/s00894-013-1943-4
dc.identifier.endpage4368en_US
dc.identifier.issn1610-2940
dc.identifier.issn0948-5023
dc.identifier.issue10en_US
dc.identifier.pmid23907552
dc.identifier.scopus2-s2.0-84884984268
dc.identifier.scopusqualityQ2
dc.identifier.startpage4349en_US
dc.identifier.urihttps://doi.org/10.1007/s00894-013-1943-4
dc.identifier.urihttps://hdl.handle.net/11468/14547
dc.identifier.volume19en_US
dc.identifier.wosWOS:000324644000028
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofJournal of Molecular Modeling
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectBinding Energiesen_US
dc.subjectComputational Modelingen_US
dc.subjectDockingen_US
dc.subjectHiv-1 Integraseen_US
dc.subjectFull-Lengthen_US
dc.subjectMm/Pbsaen_US
dc.subjectMolecular Dynamicsen_US
dc.subjectNew Inhibitorsen_US
dc.titleComputational design of a full-length model of HIV-1 integrase: modeling of new inhibitors and comparison of their calculated binding energies with those previously studieden_US
dc.titleComputational design of a full-length model of HIV-1 integrase: modeling of new inhibitors and comparison of their calculated binding energies with those previously studied
dc.typeArticleen_US

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