Brief analysis of the Hopefield-Ninio approach to kinetic proofreading

1 Brief analysis of the Hopefield-Ninio approach to kinetic proofreading 

The well-known Hopfield-Ninio scheme is usually given as the following sequence of reactions between enzyme and substrate leading to the formation of the product 

The salient features of this reaction with regard to KPR can be summarized as follows. The enzyme-substrate complex formation step involves a small amount of discrepancy (/o), whereto is the ratio of wrong and correct product formed by the enzyme. The rejection step also involves discrepancy by same amount (f,). The ATP hydrolysis rate has to be irreversible so that maximum amount of discrimination is obtained. In fact experimentally it has been proved that this assumption is true. To obtain an error fraction smaller than Vfo, more than one high-energy intermediate needs to form. The amino acid transfer rate to the tRNA, i.e., the last step, has to be very slow compared to the rejection step in the case of a wrong substrate. 

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