Reading list from 18/11/2019: fluctuation relations and some novel nucleic acid nanotech

Independent control of the thermodynamic and kinetic properties of aptamer switches
https://www.nature.com/articles/s41467-019-13137-x
Aptamers are nucleic acids strands that, by adapting a particular conformation, are able to selectively bind a sepecific molecule. The present paper proposes to modfiy the kinetics and equilbrium response of aptamers by enclosing them within a hairpin. The hairpin stem consists of a sequence of variable length, complementary to the aptamer, and linked to it by a inert poly-T linker. The length of the stem and linker provide two independent ways to tune the kinetics, response and background produced by the aptamers.

Programming molecular topologies from single-stranded nucleic acids
https://www.nature.com/articles/s41467-019-09953-w.pdf
The objective of this work is to demonstrate that the CRISPR system can be used for RNA-based gene regulation thanks to toehold-mediated strand displacement reactions. This system depends on a guide RNA that can bind to a CRISPR-associated protein. Then, the authors designed an artificial guide RNA in which binding of the protein is suppressed by occluding the handle domain of the gRNA. Only when a complementary RNA trigger molecule is expressed, the occluding domain is unfolded via toehold-mediated strand displacement. This facilitates the Cas protein binding and processing of the gRNA. With this work, it is demonstrated that strand displacement reactions can be implemented in living cells for many applications such as molecular computing, sensing, and control of bacterial gene expression.

Programmable DNA nanoindicator-based platform for Large-Scale Square Root Logic Biocomputing
https://onlinelibrary.wiley.com/doi/epdf/10.1002/smll.201903489
In the present paper, a new architecture for DNA computing in which using two types of DNA species are used: 5 3-stranded complexes that generate the different fluorescense output signals and 14 input species that are able to interact with each other, thus producing 30 different binary signals given by the same number of combinations of inputs. With this architechture, the authors are able to produce a classifier in which they code an algorithm that is able to calculate the square root of a 10-bit number being (larger than the 4 bit number that was demonstrated with the seesaw-gate-based architectures). The design requires very few species, although the new implementation relies in a higher level abstraction for the implementation with the limitations that this entails.

Thermodynamic uncertainty relations constrain non-equilibrium fluctuations
https://www.nature.com/articles/s41567-019-0702-6
A perspective on the origins and uses of a class of non-equilibrium fluctuation relations called "thermodynamic uncertainty relations". The tools of equilibrium thermodynamics enable us to calculate the properties of large equilibrium systems, circumventing any equations of motion, or other dynamical equations. These tools break down as systems are brought out of equilibrium. In non-equilibrium systems, fluctuations in observables of the system can be large (due to small system size, or external driving, perhaps). New (last 20-15 yrs) tools, called 'fluctuation theorems', can be used to calculate constraints that bound the size of these fluctuations by exploiting various symmetry arguments that hold in steady states that are out of equilibrium. The symmetries are features of the coupling between the non-equilibrium system and a large equilibrium thermodynamic reservoir (of heat, particles, charge etc.). Here, a fluctuation in the non-equilibrium system must be coupled to a near-equilibrium complementing fluctuation in the equilibrium bath, the properties of which can be calculated.

Thermodynamic uncertainty relations are the result of asking how currents (of charge, mass, chemical species, entropy) fluctuate in non-equilibrium steady states. The symmetries that underlie the exchange between the non-equilibrium system and the reservoir can be used to show that ratio of the variance of the integrated current to its mean value squared in a given time period is bounded from below by 1/(The entropy produced in the reservoir) in that time period. The authors go on to provide some examples and applications, they discuss the long-time limit of these results, and emphasise that there is much more work to be done to generalise and extend these relations. They note that constructing some hierarchy of fluctuation theorems/ relations may be beneficial in guiding the field toward unified principles.

Kinetic Proofreading and the Limits of Thermodynamic Uncertainty
https://arxiv.org/abs/1911.04673
The authors apply a thermodynamic uncertainty relation, of the type discussed above, to models of kinetic proofreading during copying via templated polymerisation. They explore system behaviour, but never really tackle the issue that thermodynamic uncertainty relations bound the predictability of the number of steps in a given time, not the accuracy with which copies are made.

Antithetic integral feedback control of monostable and oscillatory biomolecular circuits
https://www.biorxiv.org/content/10.1101/838748v1
The paper applies a mathematical method, called dominance analysis, in order to analyse the deterministic dynamics of the antithetic integral feedback controller (AIC - a molecular circuit designed to control the level of another molecular species). Dominance analysis is applied on a linear and a non-linear input network, both controlled with AIC. For fixed regions of the state-space, it has been numerically verified that AIC can give rise to stable equilibria and stable limit cycles, depending on the choice of the underlying rate coefficients.