  A long standing debate in biochemistry is to determine whether the
conformational changes observed during biomolecular interactions proceed
through conformational selection (of preexisting isoforms) or induced fit
(ligand-induced 3D reshaping). The latter mechanism had been invoked in certain
circumstances, for example to explain the non-Michaelian activity of monomeric
enzymes like glucokinase. But the relative importance of induced fit has been
recently depreciated in favor of conformational selection, assumed to be always
sufficient, predominant in general and in particular for glucokinase. The
relative contributions of conformational selection and induced fit are
reconsidered here in and out of equilibrium, in the light of earlier concepts
such as the cyclic equilibrium rule and the turning wheel of Wyman, using
single molecule state probability, one way fluxes and net fluxes. The
conditions for a switch from conformational selection to induced fit at a given
ligand concentration are explicitly determined. Out of equilibrium, the
inspection of the enzyme states circuit shows that conformational selection
alone would give a Michaelian reaction rate but not the established nonlinear
behaviour of glucokinase. Moreover, when induced fit and conformational
selection coexist and allow kinetic cooperativity, the net flux emerging in the
linkage cycle necessarily corresponds to the induced fit path.
