Unlike the case of the a-set described above, FuncLib found that the available sequence space for the b-set was comparatively broad (Table ) and that many of that many of the variants in that sequence space were predicted to be stabilizing, at least by a few kcal mol -1 , based on calculated Rosetta scores (Supplementary Data Table ). We prepared and determined Michaelis profiles of rate versus substrate concentration for the 20 variants at the top of the predicted stability ranking (Table and Supplementary Table ). Remarkably, we found a large (~50-fold) range of modulation in rate across the designed variants (Figure ), thus confirming the prediction of our chemical shift-perturbation NMR experiments that positions bearing side chains outside the active site may affect catalysis upon mutation. ) for the b-set (Figure ). Several features of the large range of rates achieved across our variants are worth noting: