Periodic Reporting for period 1 - POLINFO (Information encoding to polymers)
Período documentado: 2020-05-01 hasta 2022-04-30
The pertinence of information management in cells extends in many directions. One of the fundamental scientific questions is that of the origin of life, which remains elusive. How did life emerge from a soup of simple organic molecules swimming in the vastness of pre-biotic oceans? The famous Miller experiment from 1950s has shown that the protein building blocks, amino-acids, can be synthesized from a mixture of organic molecules under pre-biotic conditions. No equivalent experiments has been performed for the formation of nucleotides, shedding doubt as to what the first informational polymer might be.
Lately, the formation of informational polymers has taken an important role in the field of information storage to polymers. Current explosion in data acquisition and mining is one of the most influential technological advances today. Since data production is increasing exponentially, there is a need to establish alternative data storage materials in the following decade, with organic polymers, among them DNA, presenting a relevant option due to its high information density and storage energy efficiency. Currently, chains of no more than 300 subunits can be synthesized, limiting the encoding capacity of these short chains. Consequently, devising new principles that would help in the formation of informational polymers, be it organic or DNA polymers, would be of immense help for the field.
Our goal was to better understand how the formation of ordered polymers could be improved from the perspective of Physics. We use toy models to represent the formation of ordered polymers, and we aim to determine non-equilibrium conditions that would favor spontaneous ordering of sequences, which would potentially have consequences on the field of origin of life and ordered polymer synthesis.
Lately, the formation of informational polymers has taken an important role in the field of information storage to polymers. Current explosion in data acquisition and mining is one of the most influential technological advances today. Since data production is increasing exponentially, there is a need to establish alternative data storage materials in the following decade, with organic polymers, among them DNA, presenting a relevant option due to its high information density and storage energy efficiency. Currently, chains of no more than 300 subunits can be synthesized, limiting the encoding capacity of these short chains. Consequently, devising new principles that would help in the formation of informational polymers, be it organic or DNA polymers, would be of immense help for the field.
Our goal was to better understand how the formation of ordered polymers could be improved from the perspective of Physics. We use toy models to represent the formation of ordered polymers, and we aim to determine non-equilibrium conditions that would favor spontaneous ordering of sequences, which would potentially have consequences on the field of origin of life and ordered polymer synthesis.
Measuring dissipation in biochemical processes remains largely uncharted territory. Dissipation of free energy for small systems with a discrete number of species has been proposed, and successfully applied to the same family of problems, namely quantifying dissipation in the actomyosin network. The goal was to understand the connection between dissipation of energy and the information created by sequence generation during polymerization. Theory predicts that dissipation depends on the polymerization mechanism, as well as on the number of different monomers present in the simulation, even if the rates of polymerization and depolymerization of those monomers are the same. We use the free energy associated with the formation of polymer sequences, as proposed by T. Ouldridge (Ouldridge, T.E. 2021. New Journal of Physics), to quantify the free energy associated with dimer formation. Additionally, we focus primarily on the dimerization reaction, which is a good proxy for polymer synthesis where the rate of monomer addition on the chain depends only on the monomer at the end, and where the sequence does not affect the polymerization rate (Bernoulli chain). The reactions are performed in an open reactor, where two monomer types are continuously added at every time step, and where reactor content is diluted by deleting monomer compounds with a uniform rate.
Figure 1. shows the results for two non-equilibrium systems, in the first case, the rate of homodimer formation is different compared to the rate of heterodimer formation, while in the second case, the two monomers are injected at different sites. In both cases, the free energy of information is computed as a function of varying simulation parameters, and we find that the quantity is positive due to the intrinsic dependence of the distributions of dimers, fluxes, and monomers in these systems. In addition, the quantity is bound by an upper and lower value for the parameter regimes that are explored.
Figure 1. shows the results for two non-equilibrium systems, in the first case, the rate of homodimer formation is different compared to the rate of heterodimer formation, while in the second case, the two monomers are injected at different sites. In both cases, the free energy of information is computed as a function of varying simulation parameters, and we find that the quantity is positive due to the intrinsic dependence of the distributions of dimers, fluxes, and monomers in these systems. In addition, the quantity is bound by an upper and lower value for the parameter regimes that are explored.
The method was developed for the purpose of this project; a hybrid stochastic kinetics and dynamics method (ChemReactor) that allows simulating molecular conformations in a coarse-grained approach, and the simultaneous chemical reactivity of these molecules. Classical simulations generally used in biomolecular simulations do not allow for topological changes in the system. Such code can be used for a variety of problems, as chemical reactions in biology are often accompanied by and depend on molecular conformational changes.
To our knowledge, this is the first attempt to determine dissipation due to the formation of information (sequence), without the template being involved. Attempts by the Ouldrige group are so far based on information formation on a template, while we concentrate on the formation of sequences de novo, which is experimentally a much more challenging problem compared to DNA copying that is commonly found in cells or in laboratories (e.g. Polymerase Chain Reaction).
The potential societal implications of a fundamental understanding of information formation and its thermodynamic consequences are profound. This project is an attempt to contribute to the larger development of stochastic information thermodynamics, a nascent field of statistical physics.
To our knowledge, this is the first attempt to determine dissipation due to the formation of information (sequence), without the template being involved. Attempts by the Ouldrige group are so far based on information formation on a template, while we concentrate on the formation of sequences de novo, which is experimentally a much more challenging problem compared to DNA copying that is commonly found in cells or in laboratories (e.g. Polymerase Chain Reaction).
The potential societal implications of a fundamental understanding of information formation and its thermodynamic consequences are profound. This project is an attempt to contribute to the larger development of stochastic information thermodynamics, a nascent field of statistical physics.