We note that the ideal agreement between the adsorption energies calculated with QM/MM and the reference values was only observed for large cluster simulations. As illustrated in Fig. , a noticeable trend emerges where the errors in adsorption energies diminish with increasing cluster sizes, ultimately stabilizing upon reaching the 31 SBUs configuration for both UiO-66 and MOF-808. This pattern underscores the limitation of small cluster models in accurately capturing the binding energies, primarily due to their inability to fully represent the extensive range of interactions present within MOFs. Consequently, small cluster models are generally deemed insufficient for precise energy calculations, highlighting the importance of adopting larger clusters to ensure the fidelity of simulation outcomes. Comparison of QM Methods. Since the MM parameters were trained empirically with ωB97X-D, the compatibility of the P2 parameter set with alternative density functionals needs to be carefully examined. This evaluation, detailed in Table , involved calculating the RMSE and MAE for the test set to gauge the discrepancies between the adsorption energies calculated with QM/MM and the reference values across several functionals (ωB97X-D, 90 ωB97X-V, 91 B97-D, 92 M062X, and B3LYP ). Except for B3LYP, which lacks long-range dispersion interactions in the QM region, the MAE values for all other functionals remained under 2 kcal/mol. This observation suggests that the P2 parameter set is potentially compatible with a broad range of functionals, offering satisfactory accuracy.