Computational Docking Analysis for Identifying Natural Inhibitors of TEM-1 β-Lactamase

ABSTRACT

TEM-1 β-lactamase is a class A enzyme widely distributed among pathogenic bacteria and plays a major role in the hydrolysis of β-lactam antibiotics, contributing to antibiotic resistance. The present study investigated the inhibitory potential of a flavonoid-derived phytocompound against this enzyme using computational molecular docking analysis. The interaction between TEM-1 β-lactamase and Eupatin -flavonoid derived compound was evaluated and compared with the reference inhibitor Clavulanic acid. The reference inhibitor showed binding energies ranging from −4.7 to −6.5 kcal/mol, while the phytocompound demonstrated a stronger binding affinity with a docking score of approximately −7.35 kcal/mol. The ligand was found to occupy the catalytic pocket of the enzyme and formed stable interactions with key active-site residues, indicating its potential to inhibit TEM-1 β-lactamase activity. Overall, the results suggest that this phytocompound may serve as a promising lead candidate for the development of new β-lactamase inhibitors. However, additional studies such as molecular dynamics simulations, pharmacokinetic analysis, and experimental validation are required to further confirm its stability and therapeutic potential in combating β-lactamase-mediated antibiotic resistance