Computational‐Driven Theoretical Biodegradation of Antibiotics by Laccase and Underlying Aquatic Hazards Assessment

Abstract Antibiotics exert a considerable ecotoxicological impact, even at very low concentrations. However, adequately removing these substances to minimize the underlying hazards is challenging due to their hydrophilicity and strong chemical stability. To cope with this hurdle the present investigation utilized 25 antibiotics and their known human CYP metabolites (35) to evaluate ecotoxicity by implementing T.E.S.T. endpoints including; Fathead minnow (EC 50 ), Daphnia magna (LC 50 ), and Tetrahymena pyriformis (ICG 50 ). Subsequently, theoretical degradation was assessed using multivalent computational techniques coupled with Steccherinum murashkinskyi ‐derived laccase. Ecotoxicological hazards were assessed with estimated concentrations of antibiotics/metabolites ranging from 1.14E‐03 (0.00114) mg/L to 370.13 mg/L for selected endpoints. Laccase‐assisted docked complexes exhibited binding affinity in a range of −4.80 ± 0.00 to −9.40 ± 0.10 Kcal/mol (p < 0.05). Determining the accessible surface area (ΔASA) implies adequate ligand bindings. A few crucial residues; ILE, SER, PRO, THR, GLY, LEU, PHE, LYS, ALA, ASN, ASP, VAL, GLN, TRP, ARG, GLU, and HIS were identified as the most notable active site residues in the binding process. These residues contribute to various chemical interactions, including hydrogen bonds, alkyl interactions, Pi‐alkyl, Pi‐Pi T‐shaped, Pi‐Pi stacked, Pi‐anion, halogen, and Pi‐sigma type. Computational findings necessitate validation through conventional assays for practical deployment coupled with a laccase‐based system.