RuleDSD: A Rule-based Modelling and Simulation Tool for DNA Strand Displacement Systems

Prediction and Control in DNA Nanotechnology

“…Many analysis techniques used in DNA computing and molecular programming, such as chemical reaction networks and automata-theoretic models, have diffused into structural and dynamic DNA nanotechnology, inspiring diverse mechanisms for actuation, communication, and programmability while providing fundamental insights into mechanistic processes such as those involving assembly. DNA origami platforms have been used to study the dynamic behavior of DNA strand displacement (DSD) systems, ensuring the (reaction-limited) spatial locality typical of other computing models. − While TMSD is often used for actuation, ,, in DSD systems, these reactions are used to execute signal processing and control instructions , such as logic gates, fork and join gates, catalytic gates, neural network computation, and oscillators . Integration of DNA and RNA enzyme strategies has expanded the design toolbox of these nucleic acid circuits, − allowing for the design of feedback control mechanisms, predator–prey dynamics, and transcriptional oscillators, among other circuit implementations.…”

“…The system size that can be solved analytically is limited and has long since been exceeded by the complexity of experimentally implemented circuits. Modeling techniques thus play an important role in determining the state space of DSD systems, estimating signal propagation times, , and verifying if the observed behavior of a system corresponds to the behavior predicted from design . Two modeling approaches specifically stand out by virtue of their simplicity: reaction-diffusion equations and Brownian dynamics .…”

“…DNA origami platforms have been used to study the dynamic behavior of DNA strand displacement (DSD) systems, ensuring the (reaction-limited) spatial locality typical of other computing models. 144−146 While TMSD is often used for actuation, 12,24,147 in DSD systems, these reactions are used to execute signal processing and control instructions 146,148 such as logic gates, 144 fork and join gates, 149 catalytic gates, 150 neural network computation, 151 and oscillators. 152 Integration of DNA and RNA enzyme strategies has expanded the design toolbox of these nucleic acid circuits, 153−155 allowing for the design of feedback control mechanisms, 156 predator−prey dynamics, 157 and transcriptional oscillators, 158 among other circuit implementations.…”

“…Modeling techniques thus play an important role in determining the state space of DSD systems, 148 estimating signal propagation times, 159,160 and verifying if the observed behavior of a system corresponds to the behavior predicted from design. 148 Two modeling approaches specifically stand out by virtue of their simplicity: reaction-diffusion equations and Brownian dynamics. 161 The kinetics of a DSD system can be modeled as a continuous time Markov process through the state space of all possible conformations, 159 which can be characterized either by means of mathematical treatments or stochastic simulations (i.e., Monte Carlo Gillespie algorithms).…”

Formal Semantics and Verification of Network-Based Biocomputation Circuits

“…DNA walkers are molecular machines that can move along tracks [26,30] and can be used for performing computation or moving cargo for nanotechnology applications. Computational methods and tools have proven to be useful in improving and validating the designs of engineered biological systems [5,15,22] and have served as motivating applications for defining semantics and computational methods for NBC. Formal verification methods assuming discrete semantics have been used to verify the correctness of DNA Strand Displacement Systems and DNA walkers [17,31], and probabilistic model checking has also been applied to these systems [6,11,17].…”