In this section, we demonstrate the CO2 entrapment using classical unbiased MD simulation. We first model CO2 in the crystallographic position of HCO3 -for Bn86287 CA (cf. Figure ) to assess the plausibility of substrate (CO2) binding at the identical locus where the product, HCO3 -, had crystallized. Surprisingly, the CO2 migrates to the hydrophobic zone (cf. Figure ) from the crystallographic hydrophilic region (cf. Figure ) after the initial ~28 ns of simulation and stays there for the rest of the simulation time (cf. Video VS1, for detailed transformation of CO2 from one zone to another). This transition from hydrophilic to hydrophobic region can be attributed by the LIE (Linear Interaction Energy) analysis (cf. Figure ) of the enzyme-CO2 system with the evolution of time. As shown in Figure , it reveals a more negative value for the van der Waals contribution to energy (Evdw), indicating that the CO2 molecule exhibits a preference for hydrophobic interactions over the electrostatic one, thereby favoring the hydrophobic zone. . We note that in each replica, we performed a total of 100 ns simulation. Additionally, we highlight that the green and wheat segments divide the entire enzyme into two halves. (c) Energetic contribution in the total linear interaction of CO2 with surrounding amino acid during the 100 ns of MD simulation. Here, EEEL represents the electrostatic interaction energy in kcal/mol, calculated between CO2 and enzyme environment.