NOE restraints applied during CHARMM energy minimization.

Restraints were placed on key catalytic contacts, determined from previous experimental [51] and preliminary QM information. Distances between atoms were selected based on typical nonbonded interaction lengths, and spring constants were determined iteratively so that the distances were properly restrained while not over-constraining the system. kmin was the harmonic constant implemented if the interatomic distance was too small, and kmax was the harmonic constant used if the interatomic distance was too large. kminmax because catalytic contacts would remain intact at smaller distances. Entries are shown in Figure 3.