Kinetic proofreading - Wikipedia

Abstraction: Biochemical irreversible-step error-correction mechanism achieving accuracy beyond thermodynamic equilibrium limits

Key points:

• Proposed independently by John Hopfield (1974) and Jacques Ninio (1975); allows discrimination accuracy higher than the free energy difference between correct/incorrect pathways would permit
• Mechanism: an irreversible energy-consuming step preferentially ejects incorrect intermediates; specificity increases up to the ratio of exit rate constants
• Protein synthesis achieves ~1 error per 10,000 incorporations — unachievable with a one-step mechanism given the small free energy difference (~<9.2 kT) between matching and mismatching codons
• Multistep ratchet: N independent tests each with discrimination power p combine to give error rate p^N; each step requires energy input to remain irreversible
• Biological instances: aminoacyl-tRNA synthetase charging, T cell receptor antigen discrimination (via multiple phosphorylation rounds), homologous recombination (RecA), DNA damage repair
• Specificity grows exponentially with number of loops in the proofreading network; universal near-exponential completion time distribution emerges at high proofreading rates

Connections: John Hopfield · Kinetic Proofreading · Error Correction · Information Theory

Source: https://en.wikipedia.org/wiki/Kinetic_proofreading