The influence of backbone hydrogen bonds to the sulfur atom of the proximal thiolate (NH...S hydrogen bonds) on the formation of compound I in chloroperoxidase is investigated with DFT calculations. Reaction profiles for the transformation of the ferric resting state into compound I in the presence of a peroxide substrate are calculated for a model system incorporating the heme and key proximal and distal amino acid residues. We find that NH S hydrogen bonds (1) reduce the barrier for the formation of compound 0 by 7.6 kcal/mol, (2) increase the stability of compound 0 by 5.2 kcal/mol, (3) reduce the stability of compound I relative to compound 0 by 6.2 kcal/mol, and (4) reduce the stability of protonated compound 0, favoring a hybrid homo-heterolytic relative to a classic heterolytic mechanism for O-O bond scission. In general, the influence of the NH S hydrogen bonds can be traced to a reduction in the plc of the heme-bound substrate. We find that the hydrogen bond networks on the proximal and distal sides of the heme function together to modulate the mechanism of reaction. These results confirm and extend long-standing theories that the NH...S hydrogen bonds in heme thiolate proteins influence reactivity by tuning the thiolate "push" effect.