Kinetic proofreading (or kinetic amplification) is a mechanism for error correction in biochemical reactions, proposed independently by John Hopfield (1974) and Jacques Ninio (1975). Kinetic proofreading allows enzymes to discriminate between two possible reaction pathways leading to correct or incorrect products with an accuracy higher than what one would predict based on the difference in the activation energy between these two pathways.[1][2]
Increased specificity is obtained by introducing an irreversible step exiting the pathway, with reaction intermediates leading to incorrect products more likely to prematurely exit the pathway than reaction intermediates leading to the correct product. If the exit step is fast relative to the next step in the pathway, the specificity can be increased by a factor of up to the ratio between the two exit rate constants. (If the next step is fast relative to the exit step, specificity will not be increased because there will not be enough time for exit to occur.) This can be repeated more than once to increase specificity further.
As an analogy, if we have a medicine assembly line sometimes produces empty boxes, and we are unable to upgrade the assembly line, then we can increase the ratio of full boxes over empty boxes (specificity) by placing a giant fan at the end. Empty boxes are more likely to be blown off the line (a higher exit rate) than full boxes, even though both kinds' production rates are lowered. By lengthening the final section and adding more giant fans (multistep proofreading), the specificity can be increased arbitrarily, at the cost of decreasing production rate.