Conformational enhancement of fidelity in toehold-sequestered DNA nanodevices

Bader, Antoine; Cockroft, Scott L.

doi:10.1039/d0cc00882f

Cited by 7 publications

(6 citation statements)

References 53 publications

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“…Moreover, compartmentalisation means that conditions can be tuned and fuel localised to where it is required. 60,61 Through the use of high fidelity recognition motifs, DNA fuel strands can show excellent selectivity in reacting when DNA walkers reveal specific toeholds on the track, 62 leading to low background rates of unproductive fuel decomposition. 45,46 Alternatively, duplex formation between a fuel strand and a DNA machine can be used to activate a fuel to enzymatic hydrolysis 47 (Fig.…”

Section: Catalysis Of the Fuelling Reactionmentioning

confidence: 99%

Chemical fuels for molecular machinery

2022

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Chemical reaction networks that transform out-of-equilibrium 'fuel' to 'waste' are the engines that power the biomolecular machinery of the cell. Inspired by such systems, autonomous artificial molecular machinery is being developed that functions by catalysing the decomposition of chemical fuels, exploiting kinetic asymmetry to harness energy released from the fuel-to-waste reaction to drive non-equilibrium structures and dynamics. Different aspects of chemical fuels profoundly influence their ability to power molecular machines. Here we consider the structure and properties of the fuels biology has evolved and compare their features to those of the rudimentary synthetic chemical fuels that have been used to date to drive autonomous nonequilibrium molecular-level dynamics. We identify desirable, but context-specific, traits for chemical fuels together with challenges and opportunities for the design and invention of new chemical fuels to power synthetic molecular machinery and other nanoscale processes. MainFuels are consumed to provide the energy that devices and processes require to perform useful work. [1][2][3] The free energy available from a chemical reaction can be harnessed by molecular machines and dissipated to offset work performed, thus preserving the Second Law of Thermodynamics when tasks are carried out through stochastic molecular-level dynamics. 4,5 In this way chemical engines (Fig. 1) 6 transduce energy from chemical fuels and have the potential to power synthetic molecular nanotechnology 7-13 by driving and sustaining processes out-of-equilibrium. [7][8][9]14 While some synthetic molecular machines use light, 15,16 electrochemistry 17 or transmembrane gradients, 18 chemical fuels provide an attractive alternative energy source (Fig. 2). 19 Although the waste generated in chemical fuel-to-waste reactions must be dealt with (either recycled, as happens with ADP in the cell, or removed, as occurs for water and CO2 with aerobic respiration), chemical fuels are unencumbered by many of the issues faced by powering processes with other forms of energy. Photo-and electrochemistry often produce unstable intermediates, reactive radicals or cause photobleaching, all of which can limit the number of cycles that complex molecules survive for. Furthermore, in contrast to photons, chemical fuels have the potential to be stored and transported, enabling flexible and responsive systems that operate autonomously when and where they are needed. 19,20 Indeed, active organisms that require a high-density energy supply (such as animals) tend to rely exclusively on chemical energy sources, whereas photosynthesising organisms cannot harvest enough energy from sunlight to support powerintensive behaviours, such as rapid movement. The same trend is apparent in technology; lightpowered flight, for example, remains a major engineering challenge. For these and other reasons, while the energy input to biology largely originates from light (via photosynthesis), chemical fuels (such as adenosine triphosphate (ATP), Fig. 2A)...

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Section: Catalysis Of the Fuelling Reactionmentioning

confidence: 99%

Chemical fuels for molecular machinery

2022

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“…The fidelity of such devices has been improved recently. 243 The method of the previous paragraph has finite scalability in terms of serial integration since input strands get used up by sequestration during strand displacement and so lose the potency to drive the displacement equilibrium by mass action. This situation can be improved by providing a fuel strand to release input strands from their sequestered versions by a separate displacement (Fig.…”

Section: Msde Reviewmentioning

confidence: 99%

Supra-molecular agents running tasks intelligently (SMARTI): recent developments in molecular logic-based computation

Yao

Lin

Crory

et al. 2020

Mol. Syst. Des. Eng.

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“…13,14,18 To further expand the applications of EDC systems, it is highly desirable to reduce such leakages. In this regard, a number of methods, including mismatches, 24 locked nucleic acids, 25,26 terminal fraying prevention by C−G bonds, 24,27 cramps, 28 and interfering strands, 29 have been proposed to reduce leakage. These methods have been successful in partially reducing leakage, resulting in an improved apparent signal-to-noise ratio (S/N).…”

Section: ■ Introductionmentioning

confidence: 99%

Latent Toehold-Mediated DNA Circuits Based on a Bulge-Loop Structure for Leakage Reduction and Its Application to Signal-Amplifying DNA Logic Gates

Sugawara,

Oishi

2024

ACS Appl. Mater. Interfaces

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DNA circuits based on successive toehold-mediated DNA displacement reactions, particularly entropy-driven DNA circuit (EDC) systems, have attracted considerable attention as powerful enzyme-free tools for dynamic DNA nanotechnology. However, background leakage (noise signal) often occurs when the circuit is executed nonspecifically, even in the absence of the appropriate catalyst DNA (input). This study designed and developed a new latent toehold-mediated DNA circuit (LDC) system that relies on a bulge-loop structure as a latent toehold toward leakage reduction. Furthermore, the number (size) of nucleotides (nt) in the bulge-loop is found to play a significant role in the performance (i.e., leakage, signal, and kinetics) of LDC systems. In fact, the signal rate for the LDC systems increased as the number of nt in the bulge-loop increased from 4 to 8, whereas the leakage rate of the LDC systems with bulge-loops of 7 nt or less was low, but the leakage rate of the LDC system with a bulgeloop of 8 nt increased significantly. Note that the LDC system with the optimal bulge-loop (7 nt) was capable of not only reducing the leakage but also accelerating the circuit speed without any signal loss, unlike methods of reducing the leakage by reducing the signal reported previously for the conventional EDC systems. These facts indicate that the 7 nt bulge-loop acts as a "latent" toehold for the DNA circuit system. By using the amplification function of output signals with an accelerated circuit and reduced leakage, our LDC system with a 7 nt bulge-loop could be applied directly and successfully to signal-amplifying DNA logic gates such as OR and AND gates, and thus, sufficient output signals could be obtained even with a small amount of input. These findings reveal that our LDC systems with a bulge-loop structure can replace the conventional EDC system and have enormous potential in the field of DNA nanotechnology.

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Conformational enhancement of fidelity in toehold-sequestered DNA nanodevices

Abstract: Simple design principles improve conformational stability and decrease strand leakage by two orders of magnitude.

Cited by 7 publications

References 53 publications

Chemical fuels for molecular machinery

Chemical fuels for molecular machinery

Supra-molecular agents running tasks intelligently (SMARTI): recent developments in molecular logic-based computation

Latent Toehold-Mediated DNA Circuits Based on a Bulge-Loop Structure for Leakage Reduction and Its Application to Signal-Amplifying DNA Logic Gates

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