THE PRESSURE-DEPENDENCE OF HYDROPHOBIC INTERACTIONS IS CONSISTENT WITH THE OBSERVED PRESSURE DENATURATION OF PROTEINS

Proteins can be denatured by pressures of a few hundred MPa. This find ing apparently contradicts the most widely used model of protein stabi lity, where the formation of a hydrophobic core drives protein folding , The pressure denaturation puzzle is resolved by focusing on the pres sure-dependent transfer of water into the protein interior, in contras t to the transfer of nonpolar residues into water, the approach common ly taken in models of protein unfolding, Pressure denaturation of prot eins can then be explained by the pressure destabilization of hydropho bic aggregates by using an information theory model of hydrophobic int eractions, Pressure-denatured proteins, unlike heat-denatured proteins , retain a compact structure with water molecules penetrating their co re, Activation volumes for hydrophobic contributions to protein foldin g and unfolding kinetics are positive. Clathrate hydrates are predicte d to form by virtually the same mechanism that drives pressure denatur ation of proteins.