Binding interactions of Trametes villosa and Trametes lactinea laccases with 4-nonylphenol and its intermediates: molecular docking and molecular dynamics approaches

Abstract Emerging pollutants such as 4-nonylphenol (4-NP) act as endocrine disruptors and have been associated with reproductive toxicity in humans and wildlife, as well as with physiological disturbances in aquatic, terrestrial, and plant organisms. Laccases are oxidoreductases with notable biotechnological relevance and the ability to oxidize phenolic pollutants, making them attractive candidates for biodegradation strategies. This study investigated the interactions between laccases from Trametes villosa and Trametes lactinea and 4-NP and its degradation intermediates via molecular docking and molecular dynamics simulations (MDS). Ligands were geometrically optimized using the PM7 semiempirical method, and their global reactivity descriptors were computed to explore correlations between electronic properties and laccase binding affinity. Docking revealed favorable binding energies (Δ G bind ≈ −6 kcal·mol −1 ) and recurrent interactions with key amino acid residues, including Ala, Glu, Leu, Phe, Pro, Ser, Val, and His, mainly through hydrogen bonding and hydrophobic contacts. The MDS confirmed the stability of the enzyme–ligand complexes, as indicated by low root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values, along with consistent radius of gyration and solvent-accessible surface areas throughout the trajectories. Binding free energy calculations using the Molecular Mechanics/Poisson–Boltzmann Surface Area (MM/PBSA) method indicated stronger binding affinity under solvation, with Δ G bind values of −26.45 and −17.73 kcal·mol −1 for T. villosa and T. lactinea , respectively, highlighting hydrophobic and van der Waals contributions as the primary stabilizing forces. Overall, these results provide computational evidence that laccases from T. villosa and T. lactinea have potential for application in the oxidative biodegradation of 4-NP. These findings advance the molecular understanding of fungal laccase‒pollutant interactions and support future in vitro validation and protein engineering strategies aimed at enhancing biodegradation efficiency.