Simple Stochastic Simulations for Visualizing and Testing Models of Gene Expression and Proofreading*

To better visualize the stochastic nature of cellular processes and how they unfold over time, we developed a simple Gillespie algorithm to simulate two important non-equilibrium statistical processes, gene expression and translation error correction.

For example, our simulations demonstrate the concept of kinetic proofreading, generating proteins with error fractions predicted by Hopfield's rate-equation analysis, but also providing illustrative time courses for the reaction. Animations derived from simulation help build intuition. Furthermore, our simulations show that a ribosome with only kinetic proofreading, i.e. only a difference in unbinding rates between right and wrong charged tRNA, must sacrifice speed for accuracy. Simulating translation with recently measured rate constants shows how the ribosome combines kinetic proofreading, which relies on sequential, quasi-equilibrium steps, with internal discrimination, which allows for unequal forward rates, to efficiently translate mRNA with few misreadings. The stochastic simulation algorithm used here requires only a few lines of code and can easily be adapted for other biomolecular processes.

Details are available at http://biorxiv.org/cgi/content/short/418772v1