Hydration effects in protein unfolding.

The enthalpies and entropies of hydration of polar, aromatic and aliphatic groups upon unfolding of nine different globular proteins were calculated over a broad temperature range using information on the three-dimensional structures of the native states of these proteins and thermodynamic data on the transfer of various low molecular compounds modeling protein groups from the gaseous phase to water. Exclusion of these hydration effects from the calorimetrically determined enthalpy and entropy of unfolding of these proteins permitted us to estimate the energy of interactions between groups packed in the interior of the native protein, and also the entropy effects associated with the increase of configurational freedom of the backbone polypeptide chain and side chains. It is shown that the compact native state of a protein is stabilized by the enthalpic interactions between internal groups while the hydration effects of all the groups, except the aliphatic ones, which are exposed upon unfolding destabilize this state.