Application of Polymer Reaction Modeling to Nonenzymatic Polynucleotide Replication

Abstract

Methods of polymer reaction engineering were used to develop a mechanistic model of nonenzymatic polynucleotide replication. The model is made possible by the rate constants developed by Rajamani et al. This model treats the ideas of stalling proposed by Rajamani in a direct kinetic mechanism. When one assumes that multiple incorrect insertions in a row are unlikely, the model returns estimates of the error threshold very much in agreement with the modified Eigen model (based on probability arguments) proposed by Rajamani. In addition, the current model gives average lengths of poly­nucleotides, categorized by ultimate nucleoside (type and correct/incorrect) as well as the average lengths of interior and terminal sequences of correct and incorrect insertions in a row. When the insights of Leu et al. (specifically, that incorrect additions following an incorrect addition are likely) are included into the model, the error threshold will drop to unrealistic levels. To compensate for this, a mechanism for the “recycle” of incorrect strands (via hydrolysis and repolymerization) was included. Calculations indicate that even with a “correction” mechanism (hydrolysis of chain containing errors), the error threshold drops to an unacceptable value.