A solution (enzyme variant in our case) belongs to the Pareto front if there is no other variant within the set experimentally characterized with better scores in all the targeted objectives. The Pareto front identifies the subset of variants to be explored for a practical application. This is so because variants within the set experimentally characterized that do not belong to the Pareto front will be worse than those in the front in terms of both properties and, therefore, are not worth considering. For illustration, we highlight in Figure background, as least as reflected in the amount of protein obtained (Table ). This result is interesting because expression level and purification yields are biotechnologically relevant parameters which may reflect not only stability but also folding rate and, more generally, the folding landscape. In principle, the pH-dependence of the rate parameters (Figure ) is expected to be determined by the protonation of the catalytic base, which in our case is the aspartate side chain. Normal (unperturbed) pKa values for aspartic acid are about 4. Therefore, any significant pH effect on rates observed at pH values above 6 (as in Figure ) necessarily implies highly perturbed pK values for the active-site aspartic acid residues. This is, of course, reasonable as a buried aspartate in a mostly hydrophobic cavity is expected to display a perturbed pKa value substantially above 4, and elevating the pKa value of the catalytic base (e.g. through desolvation) is a common engineering strategy to enhance catalysis in Kemp eliminases and other enzymes. As discussed below, while the pH-dependence of the catalytic efficiency can be reasonably explained assuming a single perturbed pK value, that of the catalytic rate constant points to an ensemble of perturbed pKa values, in congruence with the computational analysed reported further below which suggest enhanced conformational diversity in the Michaelis complex.