arXiv subjects

Thomas E Ouldridge

Publications and source records attributed to Thomas E Ouldridge.

3 recordsLinked to original sources

arXiv2022

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

The production of sequence-specific copolymers using copolymer templates is fundamental to the synthesis of complex biological molecules and is a promising framework for the synthesis of synthetic chemical complexes. Unlike the superficially similar process of self-assembly, however, the development of synthetic systems that implement templated copying of copolymers under constant environmental conditions has been challenging. The main difficulty has been overcoming product inhibition, or the tendency of products to adhere strongly to their templates - an effect that gets exponentially stronger with template length. We develop coarse-grained models of copolymerisation on a finite-length template and analyse them through stochastic simulation. We use these models first to demonstrate that product inhibition prevents reliable template copying, and then ask how this problem can be overcome to achieve cyclic production of polymer copies of the right length and sequence in an autonomous and chemically-driven context. We find that a simple addition to the model is sufficient to generate far longer polymer products that initially form on, and then separate from, the template. In this approach, some of the free energy of polymerisation is diverted into disrupting copy-template bonds behind the leading edge of the growing copy copolymer. By additionally weakening the final copy-template bond at the end of the template, the model predicts that reliable copying with a high yield of full-length, sequence-matched products is possible over large ranges of parameter space, opening the way to the engineering of synthetic copying systems that operate autonomously.

cond-mat.soft↗

arXiv2018

The power of being explicit: demystifying work, heat, and free energy in the physics of computation

Interest in the thermodynamics of computation has revived in recent years, driven by developments in science, economics and technology. Given the consequences of the growing demand for computational power, the idea of reducing the energy cost of computations has gained new importance. Simultaneously, many biological networks are now interpreted as information-processing or computational systems constrained by their underlying thermodynamics. Indeed, some suggest that low-cost, high-density biological systems may help to mitigate the rising demand for computational power and the "end" of Moore's law of exponential growth in the density of transistors. In this chapter we address widespread misconceptions about thermodynamics and the thermodynamics of computation. In particular, we will argue against the general perception that a measurement or copy operation can be performed at no cost, against the emphasis placed on the significance of erasure operations, and against the careless discussion of heat and work. While not universal, these misconceptions are sufficiently prevalent (particularly within interdisciplinary contexts) to warrant a detailed discussion. In the process, we will argue that explicitly representing fundamental processes is a useful tool, serving to demystify key concepts. We first give a brief overview of thermodynamics, then the history of the thermodynamics of computation - particularly in terms of copy and measurement operations inherent to classic thought experiments. Subsequently, we analyse these ideas via an explicit biochemical representation of the entire cycle of Szilard's engine. In doing so we show that molecular computation is both a promising engineering paradigm, and a valuable tool in providing fundamental understanding.

cond-mat.stat-mech↗

arXiv2018

Non-equilibrium correlations in minimal dynamical models of polymer copying

Living systems produce "persistent" copies of information-carrying polymers, in which template and copy sequences remain correlated after physically decoupling. We identify a general measure of the thermodynamic efficiency with which these non-equilibrium states are created, and analyze the accuracy and efficiency of a family of dynamical models that produce persistent copies. For the weakest chemical driving, when polymer growth occurs in equilibrium, both the copy accuracy and, more surprisingly, the efficiency vanish. At higher driving strengths, accuracy and efficiency both increase, with efficiency showing one or more peaks at moderate driving. Correlations generated within the copy sequence, as well as between template and copy, store additional free energy in the copied polymer and limit the single-site accuracy for a given chemical work input. Our results provide insight in the design of natural self-replicating systems and can aid the design of synthetic replicators.

cond-mat.stat-mech↗