Catalytically active sites vibrational energy

The induction of the correct geometry in the active site of an enzyme is paid for by a good substrate, with binding energy. An alternative explanation to that of induced fit is that some small molecules (e.g., HzO in the hexokinase example) bind nonproductively, i.e., their small size allows them to assume many orientations with respect to the other substrate (ATP in the case of hexokinase) that do not lead to reaction. Large substrates are restricted in motion and are held in a catalytically correct orientation millions of times more often during molecular vibrations than is, say, water. 

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