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The\u00a0enzyme HisIE from\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>A.\u2009baumannii<\/jats:italic>\n                    <\/jats:styled-content>\n                    was explored as a therapeutic target using structure\u2010based drug design to combat bacterial infections. This study integrates various computational approaches, including homology modeling, molecular dynamics simulations (MDS), and structure\u2010based virtual screening to identify the potent inhibitors with high binding affinity and favorable pharmacokinetic properties. High\u2010throughput virtual screening of the COCONUT database identified lead compounds featuring strong binding affinities to protein targets along with favorable pharmacokinetic profiles. CNP0007442, CNP0007145, and CNP0007506 emerged as the most potent candidates based on MM\/GBSA binding free energy calculations. They exhibited stable interactions with key active site residues (His98) of\n                    <jats:italic>Ab<\/jats:italic>\n                    HisIE, primarily through Van der Waals and electrostatic forces, enabling enhanced enzyme inhibition. Furthermore, density functional theory analysis revealed optimal HOMO\u2013LUMO energy gaps, indicating the selected compounds' potential reactivity and stability. The findings highlight these candidates for further experimental validation, offering a novel therapeutic approach by disrupting the essential bacterial metabolic pathways. This study identifies promising drug\u2010like molecules targeting\n                    <jats:italic>Ab<\/jats:italic>\n                    HisIE, offering a novel strategy to combat AMR infections.\n                  <\/jats:p>","DOI":"10.1111\/apm.70070","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T02:50:11Z","timestamp":1759978211000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Unraveling the Bifunctional HisIE Enzyme in\n                    <i>Acinetobacter baumannii<\/i>\n                    JJAB01: A Novel Therapeutic Target for Combating Antimicrobial Resistance"],"prefix":"10.1111","volume":"133","author":[{"given":"Raji","family":"Rajmichael","sequence":"first","affiliation":[{"name":"Structural Biology and Bio\u2010Computing Lab, Department of Bioinformatics, Science Block Alagappa University  Karaikudi Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nagarajan","family":"Hemavathy","sequence":"additional","affiliation":[{"name":"Structural Biology and Bio\u2010Computing Lab, Department of Bioinformatics, Science Block Alagappa University  Karaikudi Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sangavi","family":"Pandi","sequence":"additional","affiliation":[{"name":"Department of Microbiology Karpagam Academy of Higher Education  Coimbatore Tamil Nadu India"},{"name":"Center for Bioinformatics Karpagam Academy of Higher Education  Coimbatore Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saritha","family":"Poopandi","sequence":"additional","affiliation":[{"name":"Structural Biology and Bio\u2010Computing Lab, Department of Bioinformatics, Science Block Alagappa University  Karaikudi Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Umashankar","family":"Vetrivel","sequence":"additional","affiliation":[{"name":"Virology &amp; 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