sentences:  Enzymes that are saturated, that is, have a high affinity substrate binding, require differential binding to reduce the energy of activation, whereas small substrate unbound enzymes may use either differential or uniform binding.These effects have led to most proteins using the differential binding mechanism to reduce the energy of activation, so most substrates have high affinity for the enzyme while in the transition state.Differential binding is carried out by the induced fit mechanism - the substrate first binds weakly, then the enzyme changes conformation increasing the affinity to the transition state and stabilizing it, so reducing the activation energy to reach it.