As shown in Figure , the overall CO2 hydration occurs with the energy expenses of 7.9 kcal/mol, demonstrating an efficient conversion CO2 to HCO3 -by metal-free CA. Interestingly, the product HCO3 -is exothermic by 12.4 kcal/mol (cf. Figure ), which further supports the experimental observations where CO2 hydration is found to be an irreversible reaction. The reaction was also tested with Tyr96 (analogous to Tyr476 of Bn86287) within all2909, and it exhibited a feasible barrier of 5.5 kcal/mol (cf. Figure ).