Simulation of non-enzymatic template-directed synthesis of oligonucleotides and peptides

A simulation model is proposed for the template- and sequence-directed (TSD) condensation of two trideoxyribonucleotide 3′-phosphate molecules into a hexameric template with palindromic sequence studied experimentally by von Kiedrowski (1986; Angew. Int. Ed. Engl. 25, 932-935). The model simulates reasonably well the kinetics of synthesis of both the template, and the pyrophosphate product which is not directly involved in the autocatalytic reaction. It offers quantitative approximation of the different rate constants of the processes involved in the reaction. The model simulates and gives predictions for the influence of factors such as the initial concentrations of the trimers and the template, and gives predictions for the effect of temperature on the dynamics of the autocatalytic reaction. The model also simulates well the production rate of a different self-replicating system (coiled coil peptide) used in the experiments of Lee et al. (1997; Nature 390, 591-594). Comparing the different rate constants, it seems that chain elongation occurs at higher rates in the peptide system (at 23°C) than in the nucleotide one (at 0°C), but that the relative contribution of template-directed synthesis is significantly larger with the nucleotides.