Computational Insights into Enzyme‐Substrate Binding Interplay Exhibit Variable Binding Attributes: A Framework for Implementing Oxidoreductase‐Based Applications

Abstract

AbstractLaccase (LAC) is a potent multicopper oxidase that relies on O2 for its catalytic activity. LAC has been affirmed as an environmentally friendly biocatalyst that often catalyzes a wide array of phenolic substrates. Bacterial‐derived LACs have been less investigated for non‐phenolic substrates in contrast to fungi‐derived LAC. To comprehend the substrates (3,4‐Dimethoxybenzyl alcohol, and Dimer (Guaiacyl 4‐O‐5 guaiacyl) binding interactions of LAC (Thermus thermophilus HB27) was carried out and contrasted with fungal‐derived Lignin peroxidase (LiP) (Trametes cervina) exploiting computational methods, including physicochemical properties, Sequence Annotated by Structure (SAS), Extra precision docking (Glide), and DESMOND‐directed MD‐ simulation. Protein structures exhibited by LAC, and LiP have diverse dissimilar component architects. The XP docking suggested LiP‐Dimer seems to have a comparatively lowest binding affinity (−8.413 kcal/mol), with an MMGBSA score of −33.249 kcal/mol. Further, docked complexes were validated leveraging 50 ns NPT system‐based MD‐simulation for structural and functional stability. The system achieved equilibrium and stability at the end of the simulation, with only the LiP‐3,4‐Dimethoxybenzyl alcohol complex maintained stability. The results of this study offer a framework for improving the binding ability of substrates by way of the use of in‐silico protein engineering, which might eventually result in more effective catalytic applications.