This discussion has thus far concentrated on the application of QM/MM methodologies for calculating adsorption energies. In this section, we extend the scope to demonstrate the effectiveness of QM/MM scheme in accurately modeling reactions in Zr-MOFs. Specifically, we focus on glucose isomerization and epimerization catalyzed by UiO-66 and MOF-808, the complete mechanism of which can be found in previous studies. Our emphasis here is on the Please do not adjust margins Please do not adjust margins which have been identified as the rate-limiting steps in glucose isomerization and epimerization, respectively. As listed in Table , the activation energies (Ea,1) for the Hshift and C-shift in glucose over UiO-66, calculated using ωB97X-D/Def2-SVP//ωB97X-D/Def2-TZVPPD, are determined to be 23.6 kcal/mol and 21.2 kcal/mol, respectively. These values are in close agreement with experimental findings, which are reported as 24.2 kcal/mol for the H-shift and 19.9 kcal/mol for the C-shift. Similarly, for MOF-808, the calculated activation energies align well with the experimental values, with the Hshift and C-shift being 24.4 kcal/mol (Ea,exp.: 23.9 kcal/mol) and 22.5 kcal/mol (Ea,exp.: 21.1 kcal/mol), respectively. These findings underscore that the P2 parameter, despite being primarily derived from adsorption energy data, is capable of accurately predicting the activation energies for reactions in MOFs. Furthermore, the accurate calculation of activation energies in MOF-808 suggests that the P2 parameters are potentially transferable to MOF-808 and other Zr-based MOFs, highlighting the versatility and broad applicability of the QM/MM(P2) approach in modeling complex reactions within MOF environments.