The Rise and Fall of the Hydrophobic Effect in Protein Folding and Protein-Protein Association, and Molecular Recognition

Abstract

In the beginning everything was explained in Biochemistry in terms of hydrogen-bonds (HB). Then, the devastating blow, known as the HB-inventory argument came; hydrogen bonding with water molecules compete with intramolecular hydrogen-bonds. As a result, the HBs paradigm fell from grace. The void created was immediately filled by Kauzmann’s idea of hydrophobic (HφO) effect which reigned supreme in biochemical literature for over 50 years (1960-2010). Cracks in the HB-inventory argument on one hand, and doubts about the adequacy of Kauzmann’s model for the HφO effect, have led to a comeback of the HBs, along with a host of new hydrophilic (HφI) effects. The HφO effects lost much of its power - which it never really had - in explaining protein folding and protein-protein association. Instead, the more powerful and richer repertoire of HφI effects took over the reins. The interactions also offered simple and straightforward answers to the problems of protein folding, and protein-protein association.