Hybrid agent-based model for quantitative in-silico cell-free protein synthesis

An advanced vision of the mRNA translation is presented through a hybrid modeling approach. The dynamics of the polysome formation was investigated by computer simulation that combined agent-based model and fine-grained Markov chain representation of the chemical kinetics. This approach allowed for the investigation of the polysome dynamics under non-steady-state and non-continuum conditions. The model is validated by the quantitative comparison of the simulation results and Luciferase protein production in cell-free system, as well as by testing of the hypothesis regarding the two possible mechanisms of the Edeine antibiotic. Calculation of the Hurst exponent demonstrated a relationship between the microscopic properties of amino acid elongation and the fractal dimension of the translation duration time series. The temporal properties of the amino acid elongation have indicated an anti-persistent behavior under low mRNA occupancy and evinced the appearance of long range interactions within the mRNA-ribosome system for high ribosome density. The dynamic and temporal characteristics of the polysomal system presented here can have a direct impact on the studies of the co-translation protein folding and provide a validated platform for cell-free system studies.