Bioinformatic and Experimental Evaluation of Compounds Targeting Acinetobacter baumannii

Abstract

Background: This study combined cheminformatics and in vitro approaches to identify novel antimicrobial compounds against Acinetobacter baumannii, a major multidrug- resistant ESKAPE pathogen.

Methods: Initially, 350 000 compounds with three-dimensional structures and specific physicochemical properties were selected from the ZINC20 database. These were further filtered using DataWarrior software based on logP, logD, polar surface area, globularity, rotatable bonds, and ionizable nitrogen groups. Molecular docking analyses targeted A. baumannii methionyl-tRNA synthetase (MetRS). One of the available molecules with the highest predicted binding affinity from the in silico analyses was evaluated for antimicrobial activity.

Results: Data curation according to the specific physicochemical properties yielded a library of 530 compounds. Docking analyses validated critical binding residues (Tyr12, Leu10, and Trp251) within the crystal structure (PDB: 5URB). Ten candidate compounds exhibited binding energies between −7.1 and −6.2 kcal/mol—approximately twice as strong as methionine. Due to stock and logistical constraints, the fourth-ranked compound (ZINC000037626221) was purchased instead of the top three. In vitro antimicrobial susceptibility testing showed minimum inhibitory concentrations of 62.5 μg/mL for A. baumannii, 125 μg/mL for Pseudomonas aeruginosa, and ≥500 μg/mL for Escherichia coli and Staphylococcus aureus.

Conclusion: The results indicate that the selected compound displayed relatively specific activity against A. baumannii compared with the other bacteria tested. Overall, the findings confirm that combining computational screening with experimental validation can effectively narrow down large chemical libraries to a manageable set of promising candidates. This integrative approach highlights the potential of MetRS as a therapeutic target and provides a framework for discovering new antimicrobial agents against multidrug-resistant Gram-negative pathogens.

Cite this article as: Mert E, Yücebağ Duranay E. Bioinformatic and experimental evaluation of compounds targeting Acinetobacter baumannii. Trends in Pharmacy, 2025, 2, 0019, doi: 10.5152/TrendsPharm.2025.25019