Thermodynamic properties of bovine pancreatic trypsin, inhibitor (BPTI) hydrated by up to 1600 water molecules, i.e., a ratio of the weight of water to that of protein, h, from 0 to similar to4.5, are studied by molecular dynamics (MD) simulation and normal-mode analysis (NMA). Temperatures range from 100 to 300 K to include the hydrated protein glass transition, T-g approximate to 200 K. The partial specific heat of BPTI computed by MD reaches fully hydrated values around h approximate to 0.7 below and above T-g. For smaller h, distinctly different variations in the apparent specific heat of BPTI with h below and above T-g are found and related to the respective decrease and increase in protein flexibility with h. Changes upon varying h in the energy landscape of hydrated BPTI near its native configuration are examined. The partial entropy of BPTI is computed with NMA up to T-g. Above 200 K, an increase in the partial entropy of BPTI is computed with specific heats of hydrated BPTI obtained by MD. The difference between the partial entropy of BPTI when fully hydrated and the entropy of dry BPTI near its native structure is computed to be 0.35 kcal/(mol K). This yields, together with the internal energy difference of -227 kcal/mol, a partial Helmholtz energy of hydrated BPTI that is lower than the Helmholtz energy of dry BPTI by 332 kcal/mol at 300 K. Coverage of BPTI by water correlates with changes in partial thermodynamic properties. A glasslike transition at similar to200 K appears in the computed specific heats when charged groups of BPTI are covered, which occurs when h approximate to 0.3. Thermodynamic properties reach fully hydrated values when there is little change with increasing h in the coverage of exposed charged and uncharged hydrophilic groups of BPTI, which occurs when h approximate to 0.7.