{"doi":"10.1007/s00894-022-05073-3","title":"Three new inhibitors of class A β-lactamases evaluated by molecular docking and dynamics simulations methods: relebactam, enmetazobactam, and QPX7728","abstract":null,"journal":"Journal of Molecular Modeling","year":2022,"id":612966,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1578735,"name":"Ayşegül Saral Sariyer","orcid":"0000-0002-7757-6812","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Three new inhibitors of class A β-lactamases evaluated by molecular docking and dynamics simulations methods: relebactam, enmetazobactam, and QPX7728","abstract":"Antibiotic-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.","is_dataset_classified":null,"base_score":1.791759469228055,"endowment":1.791759469228055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35243556","pmcid":null,"openalex_id":"https://openalex.org/W4214841347","authors":[],"funders":[],"total_grants":0,"fwci":0.2823,"citation_percentile":0.40224307,"influential_citations":0,"citation_trend":[{"year":2024,"count":3},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"closed","license":"https://www.springer.com/tdm","oa_locations":[{"url":"https://link.springer.com/content/pdf/10.1007/s00894-022-05073-3.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1007/s00894-022-05073-3/fulltext.html","host_type":"publisher"},{"url":"https://doi.org/10.1007/s00894-022-05073-3","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35243556","host_type":"repository"}],"fields_of_study":["Antibiotic Resistance in Bacteria","Computational Drug Discovery Methods","Phenothiazines and Benzothiazines Synthesis and Activities","Anti-Bacterial Agents","Azabicyclo Compounds","Borinic Acids","Carboxylic Acids","Microbial Sensitivity Tests","Molecular Docking Simulation","Triazoles","beta-Lactamases"],"mesh_terms":["Anti-Bacterial Agents","beta-Lactamases","Borinic Acids","Carboxylic Acids","Microbial Sensitivity Tests","Triazoles","Azabicyclo Compounds","Molecular Docking Simulation"],"keywords":["In silico","AutoDock","Acinetobacter baumannii","Docking (animal)","Biology","Active site","Antibiotic resistance","Molecular dynamics","Computational biology","Serine","Enzyme","Biochemistry","Microbiology","Chemistry","Pseudomonas aeruginosa","Antibiotics","Bacteria","Genetics","Gene","Computational chemistry","Medicine","Molecular docking","Molecular Dynamic Simulations","Relebactam","Class A Β-lactamases","Enmetazobactam","Qpx7728"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T05:52:34.264873Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}