Robustness against environmental changes is one of the major features of biological systems, but its origin is not well understood. We recently constructed a large-scale computational model of an Escherichia coli-based reconstituted in vitro translation system that enumerates all protein synthesis processes in detail. Our model synthesizes a formyl-Met-Gly-Gly tripeptide (MGG peptide) from 27 initial molecular components through 968 biochemical reactions. Among the 968 kinetic parameters, 483 are nonzero parameters, and the simulator was used to determine how perturbations of 483 individual reactions affect the complex reaction network. We found that even when the kinetic parameter was changed from 100- to 0.01-fold, 94% of the changes hardly affected the two indicators of reaction dynamics in MGG peptide synthesis, which represent the yield of the MGG peptide and the initial lag-time of the peptide synthesis. Moreover, none of the indicators increased proportionally to these changes: e.g., a 100-fold increase in the kinetic parameter increased the yield by only 2.2-fold at most, indicating the insensitivity of the reaction network to perturbation. Robustness and insensitivity are likely to be a common feature of large-scale biological reaction networks.
Keywords: cell-free protein synthesis; computational modeling; enzyme kinetics; network analysis; protein translation; robustness.