The invention is specific to the engineering of enzymes. The Michaelis Complex of E-S reaction is simulated using QM/MM, and MD methods. Using the QM polarized grid maps, MMPBSA. MMGBSA, low energy ES conformations that lead to the formation of attack conformation are identified. Subsequently, the enzyme is designed around the Michaelis complex where the substrate/transition states/product is low energy static conformation (Patent No: 201941016346).