Trade-Offs between Error, Speed, Noise and Energy Dissipation in Biological Processes with Proofreading

Fundamental biological processes are highly accurate because the enzymes select the correct substrate out of a pool of chemically similar substrates by activating the so-called proofreading mechanisms. Enzymes with such proofreading ability have remarkably low error rates, e.g., on the order of ~10^-8-10^-10. While the importance of such proofreading mechanisms is widely accepted, it is still not well understood if enzymes are optimized with respect to certain characteristic properties. We theoretically investigate the trade-offs between four characteristic properties for optimization, i.e., error, speed, noise and energy dissipation, using a discrete-state stochastic framework with a first-passage analysis. Two crucial biological processes are analyzed: DNA replication by T7 DNA polymerase and tRNA selection during protein translation by Escherichia Coli ribosome. We developed a quantitative method to rank the importance of the properties. It was determined that the overall reaction speed is the main optimization criterion in both systems, and the energy dissipation comes in second. I will also discuss features of the free energy landscapes that affect the characteristic properties, e.g., error rate and energy dissipation.