فهرست نشریات علمی دسترسی آزاد ایران

The rise of antibiotic resistance poses a critical threat to global health, with β-lactamase enzymes playing a central role in neutralizing β-lactam antibiotics, rendering them ineffective. Identifying novel β-lactamase inhibitors is therefore crucial for combating bacterial resistance. This study employs computational screening techniques to explore the potential of β-lactam-derived inhibitors in targeting Class D β-lactamases. A multi-stage approaches was adopted, integrating High Throughput Virtual Screening and molecular docking simulations. A ligand library containing 4891 structurally filtered β-lactam analogs from 34027 compounds was screened against eight β-lactamase proteins, employing high-throughput virtual screening, Standard Precision, and Extra Precision docking. The binding affinities were evaluated using MM-GBSA post-processing, and ADMET profiling was performed using SwissADME, pkCSM, and ADMETlab to assess pharmacokinetic properties. The results reveal that ligand 461 exhibited the highest docking score against β-lactamase protein 7VVI, suggesting strong inhibitory potential. Further interaction analysis confirmed that the identified inhibitors formed stable hydrogen-bonded complexes, enhancing their binding efficiency. Moreover, an interaction matrix demonstrated that proteins with binding affinity scores more than -5.000 kcal/mol were ineffective in hydrolyzing β-lactam antibiotics, indicating selectivity in β-lactamase function. These findings provide a foundation for the rational design of next-generation β-lactamase inhibitors, advancing the fight against antibiotic-resistant bacterial infections.