  We review the standard lock and key (LK) model for binding small ligands to
larger adsorbent molecule. We discuss three levels of the traditional LK model
for binding. Within this model the binding constant or the Gibbs energy of the
binding process is related to the total interaction energy between the ligand
and the binding site of the adsorbent molecules. When solvent molecules are
present, which is the case in all binding processes in biochemistry, we find
that a major part of the Gibbs energy of binding could be due to interactions
mediated through the solvent molecules. This finding could have major
consequences to the applicability of the LK model in drug design, and perhaps
require a shift in the prevailing paradigm in this field of research.
  Keywords: Lock and key model, Binding constant, solvent effect on binding,
hydrophilic effect, molecular recognition.
