In silico bioprospection of phenolics against penicillin binding protein (PBP1A) of Acinetobacter baumannii for interventive therapy

Infections caused by carbapenem-resistant Acinetobacter baumannii can result in death within 48 hours of hospitalization, with an overall mortality rate of about 68%. The decreased affinity of β-lactams for Penicillin-Binding Proteins 1A (PBP1A) of A. baumannii has been identified as one of its resistance mechanisms. This study utilized a structure-activity relationship pharmacophore approach complemented with molecular docking to screen a library of 12000 phenolics with affinity for PBP1A of A. baumannii. Thereafter, the top five phenolics with the most negative docking scores and efficient drug-like features relative to the reference antibiotic (imipenem) were thermodynamically evaluated through a 300-ns molecular dynamics (MD) simulation. Interestingly, the top five leads (ZINC12659587 (–25.20 kcal/mol), ZINC59466627 (–35.01 kcal/mol), ZINC04989868 (–19.67 kcal/mol), ZINC71285349 (–17.90 kcal/mol), and ZINC58836805 (–11.95 kcal/mol) had better affinity for PBP1A than imipenem (–11.50 kcal/mol) with ZINC59466627 being the most potent of the phenolics. A further probe into the structural architecture of the resulting complexes revealed that PBP1A became more compact and stable following binding the top five phenolics, with reduced amino acid residue fluctuations at its active site. In addition, except for ZINC12659587, quantum calculations using the DFT B3LYP/6-31G+(dp) revealed that the top five leads are more reactive than imipenem. While the findings from this study lent scientific credence to the profiled phenolics as modulators of PBP1A of A. baumannii , further studies using in vitro and in vivo models are underway to validate the potency of the compounds in the management of infections caused by A. baumannii [ 1 ] [ 2 ] [ 3 ]. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany