Speed, dissipation, and error in kinetic proofreading.

Abstract:

:Proofreading mechanisms increase specificity in biochemical reactions by allowing for the dissociation of intermediate complexes. These mechanisms disrupt and reset the reaction to undo errors at the cost of increased time of reaction and free energy expenditure. Here, we draw an analogy between proofreading and microtubule growth which share some of the features described above. Our analogy relates the statistics of growth and shrinkage of microtubules in physical space to the cycling of intermediate complexes in the space of chemical states in proofreading mechanisms. Using this analogy, we find a new kinetic regime of proofreading in which an exponential speed-up of the process can be achieved at the cost of a somewhat larger error rate. This regime is analogous to the transition region between two known growth regimes of microtubules (bounded and unbounded) and is sharply defined in the limit of large proofreading networks. We find that this advantageous regime of speed-error tradeoff might be present in proofreading schemes studied earlier in the charging of tRNA by tRNA synthetases, in RecA filament assembly on ssDNA, and in protein synthesis by ribosomes.

authors

Murugan A,Huse DA,Leibler S

doi

10.1073/pnas.1119911109

subject

Has Abstract

pub_date

2012-07-24 00:00:00

pages

12034-9

issue

30

eissn

0027-8424

issn

1091-6490

pii

1119911109

journal_volume

109

pub_type

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