Quantum calculations are applied to the active site of serine proteases, including four specific residues and a water molecule, as well as a substrate and proton donors in the oxyanion hole. Residues are tethered to the protein backbone of an X-ray structure but otherwise allowed to move freely to their lowest energy positions. The viability of the ring-flip hypothesis, which proposes that a 180° rotation of the His-57 imidazole ring facilitates the catalysis, is assessed by comparison of energies of configurations both before and after such a flip. Specifically considered is the contribution to catalysis of the Ser-214 residue and a water molecule that is observed in the active site. The calculations provide detailed information concerning the nature, geometry, and strength of hydrogen bonds that are formed within the active site at each stage of the enzymatic mechanism.