The starting coordinates for the geometry of the CYP450 variant were taken from the protein data bank of PDB id 5UCW and processed with MODELLER to add missing nonterminal residues. Hydrogen atoms in protein were added using the LEAP module of AMBER20 employing the ff14SB force field. Parametrization for the metal coordinated cluster (iron porphyrin and axial serine) was performed using python based AMBER20 inbuilt Metal Centre Parameter Builder tool. Since the metal coordination of the engineered P411 enzyme is different from its parent CYP450BM3 enzyme, we characterized the correct ground state geometry of the ferrous complex 2. The details of the optimized geometry can be found in the SI (c.f. Figure ). Since the triplet-state is the ground state, charges and other parameters for the subsequent MD simulations were generated for this state. The ligands tosyl azide and 4-Ethylanisole were docked in the active site of protein using AutoDock Vina , and the best pose was considered for MD simulations. The forcefield parameters for ligands were produced using a generalized AMBER force field (GAFF2) in the Antechamber module of AMBER20. The associated partial atomic charges were also generated by applying the restraint electrostatic potential (RESP) method of QM calculated charges at the HF/6-31G(d) level of theory. Subsequently, the systems were solvated in an octahedral box of TIP3P waters extending up to 10 Å from the protein surface.