Table 1. Most informative structural features predicting each kinetic constant.

For each mutant, 10 out of 100 models were selected based on the lowest total system energy. Fifty-nine structural features were calculated for the selected models and the most informative features were selected based on a constrained regularization technique (elastic net with bagging; see Methods). The table contains features that have been assigned non-zero weights during training (9 for k_cat/K_M, 8 for k_cat, 10 for K_M). The weights are multiplied by a normalized form of the value (not shown), and can therefore indicate both a positive or negative relationship. For example, a negative weight for hydrogen bonding is consistent with a positive correlation to hydrogen bonding where a smaller number indicates more hydrogen bonding is occurring. Inversely, a positive weight for packing would indicate a positive correlation since a larger value indicates a system with fewer voids. The relative contribution of each feature in determining the kinetic constant is given as a normalized weight (columns 1–3). Column 4 provides a description of each feature, and columns 5 and 6 show the range of observed values in the training dataset. The full feature table is available in S2 Table. ns = feature not selected by the algorithm.

kcat/KM	kcat	1/KM	Description	Min.	Max.
-1.00	ns	ns	Hydrogen bonding energy of pNPG	-4.53	-1.8
-0.63	1.00	-0.03	Total number of polar contacts	144	155
-0.43	ns	ns	Count of hydrogen bonds to pNPG	4	9
-0.03	ns	ns	Hydrogen bonding energy of E164	-0.93	-0.21
0.29	ns	-0.27	Lennard-Jones repulsion of Y295	0.54	0.99
0.39	0.92	ns	Change in pNPG solvent-accessible surface upon binding	0.86	0.96
0.44	0.15	1.00	Packing of the system without pNPG	0.67	0.72
0.44	0.53	0.46	Packing of the system with pNPG	0.67	0.73
0.98	0.09	ns	Hydrogen bonding energy of Y295	-1.28	-0.5
ns	-0.51	ns	Packing with pNPG around E353	0.19	1
ns	-0.10	ns	Total system energy	-636.44	-621.6
ns	-0.01	ns	Hydrogen bond energy of the total system	-76.7	-67.63
ns	ns	0.11	Lennard-Jones repulsion around E353	0.67	1.41
ns	ns	0.27	Average hydrophobic surface area without pNPG	0.51	1.75
ns	ns	0.32	Packing around E353 without pNPG	0.37	0.99
ns	ns	0.34	Packing around E164 without pNPG	0.37	0.99
ns	ns	0.38	Packing around Y295 without pNPG	0.34	0.99
ns	ns	0.51	Lennard-Jones repulsion of E164	0.83	1.53