Table 1.

Potential and binding energies of structures Fig. 3a–f.

	Ligand	Waters molecules exchangeda	Potential energy (Hartrees)b	Binding energy (kJ/mol)c
a	Urea	1	− 3140.999223	− 77.73342713
b	2-MA	1	− 3140.994208	− 64.56565459
c	Urea	2	− 3064.545142	22.46070774
d	2-MA	2	− 3064.555789	− 5.491864421
e	AHA	3	− 2988.140894	− 8.180953242
f	2-MA	3	− 2988.079474	153.0776375

^aThe number of water molecules exchanged with the ligand upon binding to the wild type active site.

^bPotential energies are quoted for the unrestricted Becke, 3-parameter, Lee–Yang–Parr (B3LYP)^47–50 functional and 6-31G*/SDD basis sets^51,52 (UB3LYP/6-31G*/SDD).

^cBinding energies were calculated as potential energy of the structure plus the potential energies of any liberated water molecules (aqueous solvation with PCM, ε = 80), minus the potential energies of the wild type active site and aqueous solvated ligand (PCM, ε = 80). All calculated energies can be found in Supplementary Table 2.