A computational QM/MM methodology for the systematic study of various structural and spectroscopic properties of strong hydrogen bonds in enzymes is presented. The theoretical model is applied to the N-delta1-H-O-delta1 hydrogen bond between His57 and Asp102 in the active sites of low-pH alpha-chymotrypsin and alpha-lytic protease. The minimum energy structures of both enzymes reproduce the experimental N-delta1-O-delta1 distance and are used to obtain computational values for the H-D fractionation factor (phi), the proton chemical shift (delta(H)) of the H-delta1, and changes in delta(H) upon isotope substitution (Deltadelta(H-D) and Adelta(H-T)). For both enzymes, calculated parameters are in good agreement with available experimental data. Predictions are made for other properties for which experimental values are not available.