for the Kemp elimination of 5-nitrobenzisoxazole by the GNCA4-WT β-lactamase (treated as the baseline 'wild-type' enzyme in this work). All values were obtained by applying the linear response approximation (LRA) to the calculated EVB trajectories, as in our previous works, and scaled assuming a dielectric constant of 4 for the highly hydrophobic environment of the de novo active site of this β-lactamase (Figure ).