Trade-Offs between Speed, Accuracy, and Dissipation in tRNAIle Aminoacylation

Abstract

AbstractLiving systems maintain a high fidelity in information processing through kinetic proofreading, a mechanism to preferentially remove incorrect substrates at the cost of energy dissipation and slower speed. Proofreading mechanisms must balance their demand for higher speed, fewer errors, and lower dissipation, but it is unclear how rates of individual reaction steps are evolutionary tuned to balance these needs, especially when multiple proofreading mechanisms are present. Here, using a discrete-state stochastic model, we analyze the optimization strategies in Escherichia coli isoleucyl-tRNA synthetase. Surprisingly, this enzyme adopts an economic proofreading strategy and improves speed and dissipation as long as the error is tolerable. Through global parameter sampling, we reveal a fundamental dissipation-error relation that bounds the enzyme’s optimal performance and explains the importance of the post-transfer editing mechanism. The proximity of native system parameters to this bound demonstrates the importance of energy dissipation as an evolutionary force affecting fitness.Graphical TOC Entry