456 research outputs found
Remote Toehold: A Mechanism for Flexible Control of DNA Hybridization Kinetics
Hybridization of DNA strands can be used to build molecular devices, and control of the kinetics of DNA hybridization is a crucial element
in the design and construction of functional and autonomous devices.
Toehold-mediated strand displacement has proved to be a powerful
mechanism that allows programmable control of DNA hybridization. So
far, attempts to control hybridization kinetics have mainly focused on
the length and binding strength of toehold sequences. Here we show that
insertion of a spacer between the toehold and displacement domains
provides additional control: modulation of the nature and length of the
spacer can be used to control strand-displacement rates over at least 3
orders of magnitude. We apply this mechanism to operate displacement
reactions in potentially useful kinetic regimes: the kinetic
proofreading and concentration-robust regimes
Modelling DNA Origami Self-Assembly at the Domain Level
We present a modelling framework, and basic model parameterization, for the
study of DNA origami folding at the level of DNA domains. Our approach is
explicitly kinetic and does not assume a specific folding pathway. The binding
of each staple is associated with a free-energy change that depends on staple
sequence, the possibility of coaxial stacking with neighbouring domains, and
the entropic cost of constraining the scaffold by inserting staple crossovers.
A rigorous thermodynamic model is difficult to implement as a result of the
complex, multiply connected geometry of the scaffold: we present a solution to
this problem for planar origami. Coaxial stacking and entropic terms,
particularly when loop closure exponents are taken to be larger than those for
ideal chains, introduce interactions between staples. These cooperative
interactions lead to the prediction of sharp assembly transitions with notable
hysteresis that are consistent with experimental observations. We show that the
model reproduces the experimentally observed consequences of reducing staple
concentration, accelerated cooling and absent staples. We also present a
simpler methodology that gives consistent results and can be used to study a
wider range of systems including non-planar origami
Designing the self-assembly of arbitrary shapes using minimal complexity building blocks
The design space for a self-assembled multicomponent objects ranges from a
solution in which every building block is unique to one with the minimum number
of distinct building blocks that unambiguously define the target structure.
Using a novel pipeline, we explore the design spaces for a set of structures of
various sizes and complexities. To understand the implications of the different
solutions, we analyse their assembly dynamics using patchy particle simulations
and study the influence of the number of distinct building blocks and the
angular and spatial tolerances on their interactions on the kinetics and yield
of the target assembly. We show that the resource-saving solution with minimum
number of distinct blocks can often assemble just as well (or faster) than
designs where each building block is unique. We further use our methods to
design multifarious structures, where building blocks are shared between
different target structures. Finally, we use coarse-grained DNA simulations to
investigate the realisation of multicomponent shapes using DNA nanostructures
as building blocks.Comment: 12 page
Robustness and modularity properties of a non-covalent DNA catalytic reaction
The biophysics of nucleic acid hybridization and strand displacement have been used for the rational design of a number of nanoscale structures and functions. Recently, molecular amplification methods have been developed in the form of non-covalent DNA catalytic reactions, in which single-stranded DNA (ssDNA) molecules catalyze the release of ssDNA product molecules from multi-stranded complexes. Here, we characterize the robustness and specificity of one such strand displacement-based catalytic reaction. We show that the designed reaction is simultaneously sensitive to sequence mutations in the catalyst and robust to a variety of impurities and molecular noise. These properties facilitate the incorporation of strand displacement-based DNA components in synthetic chemical and biological reaction networks
The Formal Language and Design Principles of Autonomous DNA Walker Circuits.
Simple computation can be performed using the interactions between single-stranded molecules of DNA. These interactions are typically toehold-mediated strand displacement reactions in a well-mixed solution. We demonstrate that a DNA circuit with tethered reactants is a distributed system and show how it can be described as a stochastic Petri net. The system can be verified by mapping the Petri net onto a continuous-time Markov chain, which can also be used to find an optimal design for the circuit. This theoretical machinery can be applied to create software that automatically designs a DNA circuit, linking an abstract propositional formula to a physical DNA computation system that is capable of evaluating it. We conclude by introducing example mechanisms that can implement such circuits experimentally and discuss their individual strengths and weaknesses
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