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The production of sequence-specific copolymers using copolymer templates isfundamental to the synthesis of complex biological molecules and is a promisingframework for the synthesis of synthetic chemical complexes. Unlike thesuperficially similar process of self-assembly, however, the development ofsynthetic systems that implement templated copying of copolymers under constantenvironmental conditions has been challenging. The main difficulty has beenovercoming product inhibition, or the tendency of products to adhere stronglyto their templates - an effect that gets exponentially stronger with templatelength. We develop coarse-grained models of copolymerisation on a finite-lengthtemplate and analyse them through stochastic simulation. We use these modelsfirst to demonstrate that product inhibition prevents reliable templatecopying, and then ask how this problem can be overcome to achieve cyclicproduction of polymer copies of the right length and sequence in an autonomousand chemically-driven context. We find that a simple addition to the model issufficient to generate far longer polymer products that initially form on, andthen separate from, the template. In this approach, some of the free energy ofpolymerisation is diverted into disrupting copy-template bonds behind theleading edge of the growing copy copolymer. By additionally weakening the finalcopy-template bond at the end of the template, the model predicts that reliablecopying with a high yield of full-length, sequence-matched products is possibleover large ranges of parameter space, opening the way to the engineering ofsynthetic copying systems that operate autonomously.

Minimal mechanism for cyclic templating of length-controlled copolymers under isothermal conditions