System setup and classical MD simulations. The structure of LiP was constructed based on the crystal structure of the native LiPH8 from P. chrysosporium (PDB entry: 1B80). Only chain A was retained in our study. The 𝛽-hydroxyl-Trp171 was converted back to a normal Trp residue. The dimeric lignin substrate was docked into the proximity of Trp171, while tartaric acid was docked into the proximity of Glu250. All dockings were performed by using the Auto-Dock Vina tool 51 in Chimera . We assigned the protonation states of titratable residues (His, Glu, Asp) based on the calculated pKa values by the PROPKA software and pH=3. The protonation states were further checked by visual inspection of the local hydrogen-bond networks. Specially, Glu250 was deprotonated, while protonation states of the other titratable residues can be found in the supporting information (SI). The general AMBER force field (GAFF) was used to model the dimeric lignin substrate and , with the atomic charges were assigned as the RESP charges at the B3LYP/6-31G(d) level of theory. The force field parameters for Cpd I and the protonated Cpd II were generated by using MCPB.py. The Amber ff14SB force field was employed to simulate the protein. Chloride ions were added to the protein surface to neutralize each system. Finally, the system was solvated in a rectangular box of TIP3P waters extending up to a minimum distance of 16 Å from the protein surface.