Water replacement hypothesis, protein

The mechanism by which these solutes exert their influence on protein stability is uncertain. The phenomenon has been extensively studied by Timasheff and his colleagues and their conclusion is that all of the protein structure-stabilising compounds are preferentially excluded from contact with the surface of the protein (Timasheff, 1982). This explanation is rather different from that invoked in the water replacement hypothesis. 

The water substitute concept states that the stabilizer replaces the water and forms hydrogen bonds with the protein, like water also does. These bonds maintain the native protein conformation and, in this way, stabilize the protein. The water substitution hypothesis has been confirmed either by spectroscopy studies (FTIR), or by experimental observations that have shown that the most efficient stabilizers are sugars which form strong hydrogen bonds with the protein. Indeed, freeze-dried systems with loss of activity present notably altered IR spectra. 

---