Three new inhibitors of class A β-lactamases evaluated by molecular docking and dynamics simulations methods: relebactam, enmetazobactam, and QPX7728

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dc.contributor.authorSaral Sarıyer, Ayşegül
dc.date.accessioned2025-10-07T11:27:12Z
dc.date.available2025-10-07T11:27:12Z
dc.date.issued2022
dc.departmentAÇÜ, Sağlık Bilimleri Fakültesi, Beslenme ve Diyetetik Bölümü
dc.description.abstractAntibiotic-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, Mycobacterium tuberculosis, Staphylococcus aureus, and Enterobacterales infections are serious global health problems, and class A β-lactamases are one mechanism that leads to antibiotic resistance. QPX7728, relebactam, and enmetazobactam are new β-lactamase inhibitors to combat β-lactam resistance. in silico approach was used in the current study to find which of the three inhibitors would be more effective for all class A β-lactamases and to reveal molecular insights into the differences between their binding energies. The mutations in conserved residues of the active sites of β-lactamases were defined using BLDB and Clustal Omega. FastME and MMseq2 were used for cluster and phylogeny analysis. 3D protein structure models for β-lactamases were built using SWISS-MODEL. ERRAT and Galaxy Web Server were used to verify 42 β-lactamase protein structures. QPX7728, relebactam, and enmetazobactam were docked to β-lactamases by using AutoDock 4.2. The TEM76-relebactam, CTX-M-81-relebactam, TEM-76-enmetazobactam, and CTX-M-200-enmetazobactam complexes were simulated by molecular dynamics method for 500 ns. Based on molecular docking results, relebactam and QPX7728 were more favorable inhibitors for serine A β-lactamases. A 2D representation of the interactions between ligands and β-lactamases showed that S235, hydrogen bonded with TEM-76, might play a role in inhibitor design. A 500-ns MD analysis of complexes indicated that distance from S70, stability in the enzyme active cavity, and high atomic displacement would account for a significant difference in inhibitor binding affinity.
dc.identifier.doi10.1007/s00894-022-05073-3
dc.identifier.issn16102940
dc.identifier.issue4
dc.identifier.scopus2-s2.0-85125691787
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://hdl.handle.net/11494/5983
dc.identifier.volume28
dc.identifier.wosWOS:000764014400001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakPubMed
dc.indekslendigikaynakScopus
dc.indekslendigikaynakWeb of Science
dc.institutionauthorSaral Sarıyer, Ayşegül
dc.language.isoen
dc.publisherSpringer Nature Link
dc.relation.ispartofJournal of Molecular Modeling
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectClass A β-lactamases
dc.subjectEnmetazobactam
dc.subjectMolecular docking
dc.subjectMolecular dynamic simulations
dc.subjectQPX7728
dc.subjectRelebactam
dc.titleThree new inhibitors of class A β-lactamases evaluated by molecular docking and dynamics simulations methods: relebactam, enmetazobactam, and QPX7728
dc.typeArticle

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