The Interplay of Heterogeneity and Product Detachment in Templated Polymer Copying

TL;DR

This study models how heterogeneity and detachment influence the efficiency and accuracy of templated polymer copying, revealing complex effects on thermodynamics and information transfer.

Contribution

It introduces a minimal model that combines heterogeneity and detachment, extending coarse-graining methods for polymerization analysis.

Findings

Heterogeneity affects copying speed and accuracy differently for correct and incorrect monomers.

Detachment prevents subdiffusive behavior near equilibrium.

Heterogeneity can enhance thermodynamic efficiency but not necessarily information transfer.

Abstract

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 heterogeniety for polymerisation speed and accuracy, but the interplay of both separation and heterogeniety 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 polymerisation to allow for heterogeneous interactions. We then show that heterogeneous copying systems with explicit detachment do not exhibit the subdiffusive behaviour 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.