The interplay of heterogeneity and product detachment in templated polymer copying

Templated copolymerization, in which information stored in the sequence of a heteropolymer template is copied into another polymer product, is the mechanism behind all known methods of genetic information transfer. A key aspect of templated copolymerization is the eventual detachment of the product from the template. A second key feature of natural biochemical systems is that the template-binding free energies of both correctly matched and incorrect monomers are heterogeneous. Previous work has considered the thermodynamic consequences of detachment and the consequences of heterogeneity for polymerization speed and accuracy, but the interplay of both separation and heterogeneity remains unexplored. In this work, we investigate a minimal model of templated copying that simultaneously incorporates both detachment from behind the leading edge of the growing copy and heterogeneous interactions. We first extend existing coarse-graining methods for models of polymerization to allow for heterogeneous interactions. We then show that heterogeneous copying systems with explicit detachment do not exhibit the subdiffusive behavior observed in the absence of detachment when near equilibrium. Next, we show that heterogeneity in correct monomer interactions tends to result in slower, less accurate copying, while heterogeneity in incorrect monomer interactions tends to result in faster, more accurate copying, due to an increased roughness in the free energy landscape of either correct or incorrect monomer pairs. Finally, we show that heterogeneity can improve on known thermodynamic efficiencies of homogeneous copying, but these increased thermodynamic efficiencies do not always translate to increased efficiencies of information transfer.