Science and Education Publishing International Journal of Physics 1 1 2013 05 08 Inversion of the Hydrophobic/Hydrophilic Paradigm Demystifies the Protein Folding and Self-Assembly of Problems 66 71 EN Arieh Ben-Naim Department of Physical Chemistry The Hebrew University of Jerusalem, Jerusalem, Israel IJP2013132 10.12691/ijp-1-3-2 2013 02 15 2013 05 05 2013 05 08 The idea that the hydrophobic effect is the major driving force for processes such as protein folding and protein-protein association has prevailed in the biochemical literature for over half a century. It has recently become clear that the evidence in favor of the hydrophobic paradigm has totally dissipated. The dominance of the hydrophobic effect has been reduced into nothing but a myth. On the other hand, the new paradigm based on a host of hydrophilic effects has emerged. This new paradigm offers simple and straightforward answers to the long sought problems of protein folding and protein-protein association.