DESTABILIZATION IS AS IMPORTANT AS BINDING

Enzymes make use of non-covalent interactions with their substrates to bring about a large fraction of their catalytic activity. These inter actions must destabilize, or increase the Gibbs energy, of the substra te in the active site in order that the transition state can be reache d easily. This destabilization may be brought about by utilization of the intrinsic binding energy between the active site and the bound sub strate by desolvation of charged groups, geometric distortion, electro static interactions and, especially, loss of entropy in the enzyme-sub strate complex. These mechanisms are described by interaction energies and require utilization of the intrinsic binding energg that is reali zed from non-covalent interactions between the enzyme and substrate. R eceptors and coupled vectorial processes, such as muscle contraction a nd active transport, utilize binding energy similarly to avoid large p eaks and valleys along the Gibbs energy profile of the reaction under physiological conditions.