13 Search Results for "Thachuk, Chris"

Document
DOI: 10.4230/LIPIcs.ISAAC.2025.7
Polynomial Equivalence of Extended Chemical Reaction Models

Authors: Divya Bajaj, Jose-Luis Castellanos, Ryan Knobel, Austin Luchsinger, Aiden Massie, Adrian Salinas, Pablo Santos, Ramiro Santos, Robert Schweller, and Tim Wylie

Published in: LIPIcs, Volume 359, 36th International Symposium on Algorithms and Computation (ISAAC 2025)

Abstract
The ability to detect whether a species (or dimension) is zero in Chemical Reaction Networks (CRN), Vector Addition Systems, or Petri Nets is known to increase the power of these models - making them capable of universal computation. While this ability may appear in many forms, such as extending the models to allow transitions to be inhibited, prioritized, or synchronized, we present an extension that directly performs this zero checking. We introduce a new void genesis CRN variant with a simple design that merely increments the count of a specific species when any other species' count goes to zero. As with previous extensions, we show that the model is Turing Universal. We then analyze several other studied CRN variants and show that they are all equivalent through a polynomial simulation with the void genesis model, which does not merely follow from Turing-universality. Thus, inhibitor species, reactions that occur at different rates, being allowed to run reactions in parallel, or even being allowed to continually add more volume to the CRN, does not add additional simulation power beyond simply detecting if a species count becomes zero.
Cite as

Divya Bajaj, Jose-Luis Castellanos, Ryan Knobel, Austin Luchsinger, Aiden Massie, Adrian Salinas, Pablo Santos, Ramiro Santos, Robert Schweller, and Tim Wylie. Polynomial Equivalence of Extended Chemical Reaction Models. In 36th International Symposium on Algorithms and Computation (ISAAC 2025). Leibniz International Proceedings in Informatics (LIPIcs), Volume 359, pp. 7:1-7:21, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2025)

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@InProceedings{bajaj_et_al:LIPIcs.ISAAC.2025.7,
  author =	{Bajaj, Divya and Castellanos, Jose-Luis and Knobel, Ryan and Luchsinger, Austin and Massie, Aiden and Salinas, Adrian and Santos, Pablo and Santos, Ramiro and Schweller, Robert and Wylie, Tim},
  title =	{{Polynomial Equivalence of Extended Chemical Reaction Models}},
  booktitle =	{36th International Symposium on Algorithms and Computation (ISAAC 2025)},
  pages =	{7:1--7:21},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-408-6},
  ISSN =	{1868-8969},
  year =	{2025},
  volume =	{359},
  editor =	{Chen, Ho-Lin and Hon, Wing-Kai and Tsai, Meng-Tsung},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.ISAAC.2025.7},
  URN =		{urn:nbn:de:0030-drops-249158},
  doi =		{10.4230/LIPIcs.ISAAC.2025.7},
  annote =	{Keywords: Chemical Reaction Networks, Simulations, Petri-nets, Vector Addition Systems, Bi-simulation, Turing-universality, Inhibitors}
}
Document
DOI: 10.4230/LIPIcs.GD.2025.35
A Walk on the Wild Side: A Shape-First Methodology for Orthogonal Drawings

Authors: Giordano Andreola, Susanna Caroppo, Giuseppe Di Battista, Fabrizio Grosso, Maurizio Patrignani, and Allegra Strippoli

Published in: LIPIcs, Volume 357, 33rd International Symposium on Graph Drawing and Network Visualization (GD 2025)

Abstract
Several algorithms for the construction of orthogonal drawings of graphs, including those based on the Topology-Shape-Metrics (TSM) paradigm, tend to prioritize the minimization of crossings. This emphasis has two notable side effects: some edges are drawn with unnecessarily long sequences of segments and bends, and the overall drawing area may become excessively large. As a result, the produced drawings often lack geometric uniformity. Moreover, orthogonal crossings are known to have a limited impact on readability, suggesting that crossing minimization may not always be the optimal goal. In this paper, we introduce a methodology that "subverts" the traditional TSM pipeline by focusing on minimizing bends. Given a graph G, we ideally seek to construct a rectilinear drawing of G, that is, an orthogonal drawing with no bends. When not possible, we incrementally subdivide the edges of G by introducing dummy vertices that will (possibly) correspond to bends in the final drawing. This process continues until a rectilinear drawing of a subdivision of the graph is found, after which the final coordinates are computed. We tackle the (NP-complete) rectilinear drawability problem by encoding it as a SAT formula and solving it with state-of-the-art SAT solvers. If the SAT formula is unsatisfiable, we use the solver’s proof to determine which edge to subdivide. Our implementation, domus, which is fairly simple, is evaluated through extensive experiments on small- to medium-sized graphs. The results show that it consistently outperforms ogdf’s TSM-based approach across most standard graph drawing metrics.
Cite as

Giordano Andreola, Susanna Caroppo, Giuseppe Di Battista, Fabrizio Grosso, Maurizio Patrignani, and Allegra Strippoli. A Walk on the Wild Side: A Shape-First Methodology for Orthogonal Drawings. In 33rd International Symposium on Graph Drawing and Network Visualization (GD 2025). Leibniz International Proceedings in Informatics (LIPIcs), Volume 357, pp. 35:1-35:20, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2025)

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@InProceedings{andreola_et_al:LIPIcs.GD.2025.35,
  author =	{Andreola, Giordano and Caroppo, Susanna and Di Battista, Giuseppe and Grosso, Fabrizio and Patrignani, Maurizio and Strippoli, Allegra},
  title =	{{A Walk on the Wild Side: A Shape-First Methodology for Orthogonal Drawings}},
  booktitle =	{33rd International Symposium on Graph Drawing and Network Visualization (GD 2025)},
  pages =	{35:1--35:20},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-403-1},
  ISSN =	{1868-8969},
  year =	{2025},
  volume =	{357},
  editor =	{Dujmovi\'{c}, Vida and Montecchiani, Fabrizio},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.GD.2025.35},
  URN =		{urn:nbn:de:0030-drops-250218},
  doi =		{10.4230/LIPIcs.GD.2025.35},
  annote =	{Keywords: Non-planar Orthogonal Drawings, SAT Solver, Experimental Comparison}
}
Document
DOI: 10.4230/LIPIcs.DNA.31.1
Algorithmic Hardness of the Partition Function for Nucleic Acid Strands

Authors: Gwendal Ducloz, Ahmed Shalaby, and Damien Woods

Published in: LIPIcs, Volume 347, 31st International Conference on DNA Computing and Molecular Programming (DNA 31) (2025)

Abstract
To understand and engineer biological and artificial nucleic acid systems, algorithms are employed for prediction of secondary structures at thermodynamic equilibrium. Dynamic programming algorithms are used to compute the most favoured, or Minimum Free Energy (MFE), structure, and the Partition Function (PF) - a tool for assigning a probability to any structure. However, in some situations, such as when there are large numbers of strands, or pseudoknotted systems, NP-hardness results show that such algorithms are unlikely, but only for MFE. Curiously, algorithmic hardness results were not shown for PF, leaving two open questions on the complexity of PF for multiple strands and single strands with pseudoknots. The challenge is that while the MFE problem cares only about one, or a few structures, PF is a summation over the entire secondary structure space, giving theorists the vibe that computing PF should not only be as hard as MFE, but should be even harder. We answer both questions. First, we show that computing PF is #P-hard for systems with an unbounded number of strands, answering a question of Condon Hajiaghayi, and Thachuk [DNA27]. Second, for even a single strand, but allowing pseudoknots, we find that PF is #P-hard. Our proof relies on a novel magnification trick that leads to a tightly-woven set of reductions between five key thermodynamic problems: MFE, PF, their decision versions, and #SSEL that counts structures of a given energy. Our reductions show these five problems are fundamentally related for any energy model amenable to magnification. That general classification clarifies the mathematical landscape of nucleic acid energy models and yields several open questions.
Cite as

Gwendal Ducloz, Ahmed Shalaby, and Damien Woods. Algorithmic Hardness of the Partition Function for Nucleic Acid Strands. In 31st International Conference on DNA Computing and Molecular Programming (DNA 31). Leibniz International Proceedings in Informatics (LIPIcs), Volume 347, pp. 1:1-1:23, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2025)

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@InProceedings{ducloz_et_al:LIPIcs.DNA.31.1,
  author =	{Ducloz, Gwendal and Shalaby, Ahmed and Woods, Damien},
  title =	{{Algorithmic Hardness of the Partition Function for Nucleic Acid Strands}},
  booktitle =	{31st International Conference on DNA Computing and Molecular Programming (DNA 31)},
  pages =	{1:1--1:23},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-399-7},
  ISSN =	{1868-8969},
  year =	{2025},
  volume =	{347},
  editor =	{Schaeffer, Josie and Zhang, Fei},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.DNA.31.1},
  URN =		{urn:nbn:de:0030-drops-238504},
  doi =		{10.4230/LIPIcs.DNA.31.1},
  annote =	{Keywords: Partition function, minimum free energy, nucleic acid, DNA, RNA, secondary structure, computational complexity, #P-hardness}
}
Document
DOI: 10.4230/LIPIcs.DNA.31.2
A Coupled Reconfiguration Mechanism That Enables Powerful, Pseudoknot-Robust DNA Strand Displacement Devices with 2-Stranded Inputs

Authors: Hope Amber Johnson and Anne Condon

Published in: LIPIcs, Volume 347, 31st International Conference on DNA Computing and Molecular Programming (DNA 31) (2025)

Abstract
DNA strand displacement, a collective name for certain behaviors of short strands of DNA, has been used to build many interesting molecular devices over the past few decades. Among those devices are general implementation schemes for Chemical Reaction Networks, suggesting a place in an abstraction hierarchy for complex molecular programming. However, the possibilities of DNA strand displacement are far from fully explored. On a theoretical level, most DNA strand displacement systems are built out of a few simple motifs, with the space of possible motifs otherwise unexplored. On a practical level, the desire for general, large-scale DNA strand displacement systems is not fulfilled. Those systems that are scalable are not general, and those that are general don't scale up well. We have recently been exploring the space of possibilities for DNA strand displacement systems where all input complexes are made out of at most two strands of DNA. As a test case, we've had an open question of whether such systems can implement general Chemical Reaction Networks, in a way that has a certain set of other desirable properties - reversible, systematic, O(1) toeholds, bimolecular reactions, and correct according to CRN bisimulation - that the state-of-the-art implementations with more than 2-stranded inputs have. Until now we've had a few results that have all but one of those desirable properties, including one based on a novel mechanism we called coupled reconfiguration, but that depended on the physically questionable assumption that pseudoknots cannot occur. We wondered whether the same type of mechanism could be done in a pseudoknot-robust way. In this work we show that in fact, coupled reconfiguration can be done in a pseudoknot-robust way, and this mechanism can implement general Chemical Reaction Networks with all inputs being single strands of DNA. Going further, the same motifs used in this mechanism can implement stacks and surface-based bimolecular reactions. Those have been previously studied as part of polymer extensions of the Chemical Reaction Network model, and on an abstract model level, the resulting extensions are Turing-complete in ways the base Chemical Reaction Network model is not. Our mechanisms are significantly different from previously tested DNA strand displacement systems, which raises questions about their ability to be implemented experimentally, but we have some reasons to believe the challenges are solvable. So we present the pseudoknot-robust coupled reconfiguration mechanism and its use for general Chemical Reaction Network implementations; we present the extensions of the mechanism to stack and surface reactions; and we discuss the possible obstacles and solutions to experimental implementation, as well as the theoretical implications of this mechanism.
Cite as

Hope Amber Johnson and Anne Condon. A Coupled Reconfiguration Mechanism That Enables Powerful, Pseudoknot-Robust DNA Strand Displacement Devices with 2-Stranded Inputs. In 31st International Conference on DNA Computing and Molecular Programming (DNA 31). Leibniz International Proceedings in Informatics (LIPIcs), Volume 347, pp. 2:1-2:23, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2025)

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@InProceedings{johnson_et_al:LIPIcs.DNA.31.2,
  author =	{Johnson, Hope Amber and Condon, Anne},
  title =	{{A Coupled Reconfiguration Mechanism That Enables Powerful, Pseudoknot-Robust DNA Strand Displacement Devices with 2-Stranded Inputs}},
  booktitle =	{31st International Conference on DNA Computing and Molecular Programming (DNA 31)},
  pages =	{2:1--2:23},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-399-7},
  ISSN =	{1868-8969},
  year =	{2025},
  volume =	{347},
  editor =	{Schaeffer, Josie and Zhang, Fei},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.DNA.31.2},
  URN =		{urn:nbn:de:0030-drops-238514},
  doi =		{10.4230/LIPIcs.DNA.31.2},
  annote =	{Keywords: Molecular programming, DNA strand displacement, Chemical Reaction Networks}
}
Document
DOI: 10.4230/LIPIcs.DNA.31.3
Reachability in Deletion-Only Chemical Reaction Networks

Authors: Bin Fu, Timothy Gomez, Ryan Knobel, Austin Luchsinger, Aiden Massie, Marco Rodriguez, Adrian Salinas, Robert Schweller, and Tim Wylie

Published in: LIPIcs, Volume 347, 31st International Conference on DNA Computing and Molecular Programming (DNA 31) (2025)

Abstract
For general discrete Chemical Reaction Networks (CRNs), the fundamental problem of reachability - the question of whether a target configuration can be produced from a given initial configuration - was recently shown to be Ackermann-complete. However, many open questions remain about which features of the CRN model drive this complexity. We study a restricted class of CRNs with void rules, reactions that only decrease species counts. We further examine this regime in the motivated model of step CRNs, which allow additional species to be introduced in discrete stages. With and without steps, we characterize the complexity of the reachability problem for CRNs with void rules. We show that, without steps, reachability remains polynomial-time solvable for bimolecular systems but becomes NP-complete for larger reactions. Conversely, with just a single step, reachability becomes NP-complete even for bimolecular systems. Our results provide a nearly complete classification of void-rule reachability problems into tractable and intractable cases, with only a single exception.
Cite as

Bin Fu, Timothy Gomez, Ryan Knobel, Austin Luchsinger, Aiden Massie, Marco Rodriguez, Adrian Salinas, Robert Schweller, and Tim Wylie. Reachability in Deletion-Only Chemical Reaction Networks. In 31st International Conference on DNA Computing and Molecular Programming (DNA 31). Leibniz International Proceedings in Informatics (LIPIcs), Volume 347, pp. 3:1-3:21, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2025)

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@InProceedings{fu_et_al:LIPIcs.DNA.31.3,
  author =	{Fu, Bin and Gomez, Timothy and Knobel, Ryan and Luchsinger, Austin and Massie, Aiden and Rodriguez, Marco and Salinas, Adrian and Schweller, Robert and Wylie, Tim},
  title =	{{Reachability in Deletion-Only Chemical Reaction Networks}},
  booktitle =	{31st International Conference on DNA Computing and Molecular Programming (DNA 31)},
  pages =	{3:1--3:21},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-399-7},
  ISSN =	{1868-8969},
  year =	{2025},
  volume =	{347},
  editor =	{Schaeffer, Josie and Zhang, Fei},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.DNA.31.3},
  URN =		{urn:nbn:de:0030-drops-238521},
  doi =		{10.4230/LIPIcs.DNA.31.3},
  annote =	{Keywords: CRN, Chemical Reaction Network, Reachability, Void Reactions}
}
Document
DOI: 10.4230/LIPIcs.DNA.31.10
Computing and Bounding Equilibrium Concentrations in Athermic Chemical Systems

Authors: Hamidreza Akef, Minki Hhan, and David Soloveichik

Published in: LIPIcs, Volume 347, 31st International Conference on DNA Computing and Molecular Programming (DNA 31) (2025)

Abstract
Computing equilibrium concentrations of molecular complexes is generally analytically intractable and requires numerical approaches. In this work we focus on the polymer-monomer level, where indivisible molecules (monomers) combine to form complexes (polymers). Rather than employing free-energy parameters for each polymer, we focus on the athermic setting where all interactions preserve enthalpy. This setting aligns with the strongly bonded (domain-based) regime in DNA nanotechnology when strands can bind in different ways, but always with maximum overall bonding - and is consistent with the saturated configurations in the Thermodynamic Binding Networks (TBNs) model. Within this context, we develop an iterative algorithm for assigning polymer concentrations to satisfy detailed-balance, where on-target (desired) polymers are in high concentrations and off-target (undesired) polymers are in low. Even if not directly executed, our algorithm provides effective insights into upper bounds on concentration of off-target polymers, connecting combinatorial arguments about discrete configurations such as those in the TBN model to real-valued concentrations. We conclude with an application of our method to decreasing leak in DNA logic and signal propagation. Our results offer a new framework for design and verification of equilibrium concentrations when configurations are distinguished by entropic forces.
Cite as

Hamidreza Akef, Minki Hhan, and David Soloveichik. Computing and Bounding Equilibrium Concentrations in Athermic Chemical Systems. In 31st International Conference on DNA Computing and Molecular Programming (DNA 31). Leibniz International Proceedings in Informatics (LIPIcs), Volume 347, pp. 10:1-10:19, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2025)

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@InProceedings{akef_et_al:LIPIcs.DNA.31.10,
  author =	{Akef, Hamidreza and Hhan, Minki and Soloveichik, David},
  title =	{{Computing and Bounding Equilibrium Concentrations in Athermic Chemical Systems}},
  booktitle =	{31st International Conference on DNA Computing and Molecular Programming (DNA 31)},
  pages =	{10:1--10:19},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-399-7},
  ISSN =	{1868-8969},
  year =	{2025},
  volume =	{347},
  editor =	{Schaeffer, Josie and Zhang, Fei},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.DNA.31.10},
  URN =		{urn:nbn:de:0030-drops-238595},
  doi =		{10.4230/LIPIcs.DNA.31.10},
  annote =	{Keywords: Equilibrium concentrations, Thermodynamic Binding Networks, Monomer-polymer model, Detailed balance}
}
Document
DOI: 10.4230/LIPIcs.DNA.31.11
Leakless Polymerase-Dependent Strand Displacement Systems

Authors: Zoë Evelyn Mōhalakealoha Derauf and Chris Thachuk

Published in: LIPIcs, Volume 347, 31st International Conference on DNA Computing and Molecular Programming (DNA 31) (2025)

Abstract
A grand challenge facing molecular programmers is the rational development of fast, robust, and isothermal architectures akin to "chemical central processing units" that can sense (bio-)chemical signals from their environment, perform complex computation, and orchestrate a physical response in situ. DNA strand displacement systems (DSDs) remain a compelling candidate, but are hampered by spurious reaction pathways that lead to incorrect output. DSDs that utilize the systematic leakless motif can be made arbitrarily robust at the cost of increasing redundancy and network size (scaling), and thus a degradation of kinetic performance. Another class of architectures utilize DNA hybridization, extension, and signal production of entirely sequestered outputs via strand-displacing polymerases (SDPs) that have resulted in impressive demonstrations; however, they face similar challenges of aberrant behavior such as mis-priming by incorrect signals. Our work introduces a unified polymerase-dependent toehold-mediated strand displacement (PD-TMSD) architecture that integrates the programmed specificity of DSDs with the unique advantages of SDPs. This unification enables systems that can be made arbitrarily robust, at any concentration range, without increasing network size. We propose a number of gate designs and composition rules to compute arbitrary Boolean functions, emulate arbitrary chemical reaction networks, and explore time-bounded probabilistic computation made possible by certain classes of SDPs. Our theoretical exploration is backed by preliminary experimental demonstrations. This contribution was inspired by the belief that molecular programming can meet or exceed the complexity exhibited in biology if we embrace its best understood molecular machinery and couple it with systematic design principles built upon a strong theoretical foundation.
Cite as

Zoë Evelyn Mōhalakealoha Derauf and Chris Thachuk. Leakless Polymerase-Dependent Strand Displacement Systems. In 31st International Conference on DNA Computing and Molecular Programming (DNA 31). Leibniz International Proceedings in Informatics (LIPIcs), Volume 347, pp. 11:1-11:19, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2025)

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@InProceedings{derauf_et_al:LIPIcs.DNA.31.11,
  author =	{Derauf, Zo\"{e} Evelyn M\={o}halakealoha and Thachuk, Chris},
  title =	{{Leakless Polymerase-Dependent Strand Displacement Systems}},
  booktitle =	{31st International Conference on DNA Computing and Molecular Programming (DNA 31)},
  pages =	{11:1--11:19},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-399-7},
  ISSN =	{1868-8969},
  year =	{2025},
  volume =	{347},
  editor =	{Schaeffer, Josie and Zhang, Fei},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.DNA.31.11},
  URN =		{urn:nbn:de:0030-drops-238608},
  doi =		{10.4230/LIPIcs.DNA.31.11},
  annote =	{Keywords: DNA strand displacement, strand-displacing polymerases, molecular computation, energy barriers, kinetics}
}
Document
Track A: Algorithms, Complexity and Games
DOI: 10.4230/LIPIcs.ICALP.2025.130
An Efficient Algorithm to Compute the Minimum Free Energy of Interacting Nucleic Acid Strands

Authors: Ahmed Shalaby and Damien Woods

Published in: LIPIcs, Volume 334, 52nd International Colloquium on Automata, Languages, and Programming (ICALP 2025)

Abstract
The information-encoding molecules RNA and DNA bind via base pairing to form an exponentially large set of secondary structures. Practitioners need algorithms to predict the most favoured structures, called minimum free energy (MFE) structures, or to compute a partition function that allows assigning a probability to any structure. MFE prediction is NP-hard in the presence pseudoknots - base pairings that violate a restricted planarity condition. However, for single-stranded unpseudoknotted structures, there are polynomial time dynamic programming algorithms. For multiple strands, the problem is significantly more complicated: Codon, Hajiaghayi and Thachuk [DNA27, 2021] proved it NP-hard for N bases and 𝒪(N) strands. Dirks, Bois, Schaeffer, Winfree and Pierce [SIAM Review, 2007] gave a polynomial time partition function algorithm for multiple (𝒪(1)) strands, now widely-used, however their technique did not generalise to MFE which they left open. We give an 𝒪(N⁴) time algorithm for unpseudoknotted multiple (𝒪(1)) strand MFE prediction, answering the open problem from Dirks et al. The challenge lies in considering the rotational symmetry of secondary structures, a global feature not immediately amenable to local subproblem decomposition used in dynamic programming. Our proof has two main technical contributions: First, a characterisation of symmetric secondary structures implying only quadratically many need to be considered when computing the rotational symmetry penalty. Second, that bound is leveraged by a backtracking algorithm to efficiently find the MFE in an exponential space of contenders.
Cite as

Ahmed Shalaby and Damien Woods. An Efficient Algorithm to Compute the Minimum Free Energy of Interacting Nucleic Acid Strands. In 52nd International Colloquium on Automata, Languages, and Programming (ICALP 2025). Leibniz International Proceedings in Informatics (LIPIcs), Volume 334, pp. 130:1-130:20, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2025)

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@InProceedings{shalaby_et_al:LIPIcs.ICALP.2025.130,
  author =	{Shalaby, Ahmed and Woods, Damien},
  title =	{{An Efficient Algorithm to Compute the Minimum Free Energy of Interacting Nucleic Acid Strands}},
  booktitle =	{52nd International Colloquium on Automata, Languages, and Programming (ICALP 2025)},
  pages =	{130:1--130:20},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-372-0},
  ISSN =	{1868-8969},
  year =	{2025},
  volume =	{334},
  editor =	{Censor-Hillel, Keren and Grandoni, Fabrizio and Ouaknine, Jo\"{e}l and Puppis, Gabriele},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.ICALP.2025.130},
  URN =		{urn:nbn:de:0030-drops-235071},
  doi =		{10.4230/LIPIcs.ICALP.2025.130},
  annote =	{Keywords: Minimum free energy, MFE, partition function, nucleic acid, DNA, RNA, secondary structure, computational complexity, algorithm analysis and design, dynamic programming}
}
Document
Brief Announcement
DOI: 10.4230/LIPIcs.SAND.2025.23
Brief Announcement: Reachability in Deletion-Only Chemical Reaction Networks

Authors: Bin Fu, Timothy Gomez, Ryan Knobel, Austin Luchsinger, Aiden Massie, Marco Rodriguez, Adrian Salinas, Robert Schweller, and Tim Wylie

Published in: LIPIcs, Volume 330, 4th Symposium on Algorithmic Foundations of Dynamic Networks (SAND 2025)

Abstract
For general discrete Chemical Reaction Networks (CRNs), the fundamental problem of reachability - the question of whether a target configuration can be produced from a given initial configuration - was recently shown to be Ackermann-complete. However, many open questions remain about which features of the CRN model drive this complexity. We study a restricted class of CRNs with void rules, reactions that only decrease species counts. We further examine this regime in the motivated model of step CRNs, which allow additional species to be introduced in discrete stages. With and without steps, we characterize the complexity of the reachability problem for CRNs with void rules. We show that, without steps, reachability remains polynomial-time solvable for bimolecular systems but becomes NP-complete for larger reactions. Conversely, with just a single step, reachability becomes NP-complete even for bimolecular systems. Beyond what is contained in this brief announcement, we also investigate optimization variants of reachability, provide approximation results for maximizing species deletion, establish ETH-based lower bounds for NP-complete cases, and prove hardness for counting reaction sequences.
Cite as

Bin Fu, Timothy Gomez, Ryan Knobel, Austin Luchsinger, Aiden Massie, Marco Rodriguez, Adrian Salinas, Robert Schweller, and Tim Wylie. Brief Announcement: Reachability in Deletion-Only Chemical Reaction Networks. In 4th Symposium on Algorithmic Foundations of Dynamic Networks (SAND 2025). Leibniz International Proceedings in Informatics (LIPIcs), Volume 330, pp. 23:1-23:6, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2025)

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@InProceedings{fu_et_al:LIPIcs.SAND.2025.23,
  author =	{Fu, Bin and Gomez, Timothy and Knobel, Ryan and Luchsinger, Austin and Massie, Aiden and Rodriguez, Marco and Salinas, Adrian and Schweller, Robert and Wylie, Tim},
  title =	{{Brief Announcement: Reachability in Deletion-Only Chemical Reaction Networks}},
  booktitle =	{4th Symposium on Algorithmic Foundations of Dynamic Networks (SAND 2025)},
  pages =	{23:1--23:6},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-368-3},
  ISSN =	{1868-8969},
  year =	{2025},
  volume =	{330},
  editor =	{Meeks, Kitty and Scheideler, Christian},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.SAND.2025.23},
  URN =		{urn:nbn:de:0030-drops-230768},
  doi =		{10.4230/LIPIcs.SAND.2025.23},
  annote =	{Keywords: CRN, Chemical Reaction Network, Reachability, Void Reactions}
}
Document
DOI: 10.4230/LIPIcs.DNA.29.1
Minimum Free Energy, Partition Function and Kinetics Simulation Algorithms for a Multistranded Scaffolded DNA Computer

Authors: Ahmed Shalaby, Chris Thachuk, and Damien Woods

Published in: LIPIcs, Volume 276, 29th International Conference on DNA Computing and Molecular Programming (DNA 29) (2023)

Abstract
Polynomial time dynamic programming algorithms play a crucial role in the design, analysis and engineering of nucleic acid systems including DNA computers and DNA/RNA nanostructures. However, in complex multistranded or pseudoknotted systems, computing the minimum free energy (MFE), and partition function of nucleic acid systems is NP-hard. Despite this, multistranded and/or pseudoknotted systems represent some of the most utilised and successful systems in the field. This leaves open the tempting possibility that many of the kinds of multistranded and/or pseudoknotted systems we wish to engineer actually fall into restricted classes, that do in fact have polynomial time algorithms, but we've just not found them yet. Here, we give polynomial time algorithms for MFE and partition function calculation for a restricted kind of multistranded system called the 1D scaffolded DNA computer. This model of computation thermodynamically favours correct outputs over erroneous states, simulates finite state machines in 1D and Boolean circuits in 2D, and is amenable to DNA storage applications. In an effort to begin to ask the question of whether we can naturally compare the expressivity of nucleic acid systems based on the computational complexity of prediction of their preferred energetic states, we show our MFE problem is in logspace (the complexity class L), making it perhaps one of the simplest known, natural, nucleic acid MFE problems. Finally, we provide a stochastic kinetic simulator for the 1D scaffolded DNA computer and evaluate strategies for efficiently speeding up this thermodynamically favourable system in a constant-temperature kinetic regime.
Cite as

Ahmed Shalaby, Chris Thachuk, and Damien Woods. Minimum Free Energy, Partition Function and Kinetics Simulation Algorithms for a Multistranded Scaffolded DNA Computer. In 29th International Conference on DNA Computing and Molecular Programming (DNA 29). Leibniz International Proceedings in Informatics (LIPIcs), Volume 276, pp. 1:1-1:22, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2023)

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@InProceedings{shalaby_et_al:LIPIcs.DNA.29.1,
  author =	{Shalaby, Ahmed and Thachuk, Chris and Woods, Damien},
  title =	{{Minimum Free Energy, Partition Function and Kinetics Simulation Algorithms for a Multistranded Scaffolded DNA Computer}},
  booktitle =	{29th International Conference on DNA Computing and Molecular Programming (DNA 29)},
  pages =	{1:1--1:22},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-297-6},
  ISSN =	{1868-8969},
  year =	{2023},
  volume =	{276},
  editor =	{Chen, Ho-Lin and Evans, Constantine G.},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.DNA.29.1},
  URN =		{urn:nbn:de:0030-drops-187840},
  doi =		{10.4230/LIPIcs.DNA.29.1},
  annote =	{Keywords: thermodynamic computation, model of computation, molecular computing, minimum free energy, partition function, DNA computing, DNA self-assembly, DNA strand displacement, kinetics simulation}
}
Document
DOI: 10.4230/LIPIcs.DNA.28.1
Fast and Robust Strand Displacement Cascades via Systematic Design Strategies

Authors: Tiernan Kennedy, Cadence Pearce, and Chris Thachuk

Published in: LIPIcs, Volume 238, 28th International Conference on DNA Computing and Molecular Programming (DNA 28) (2022)

Abstract
A barrier to wider adoption of molecular computation is the difficulty of implementing arbitrary chemical reaction networks (CRNs) that are robust and replicate the kinetics of designed behavior. DNA Strand Displacement (DSD) cascades have been a favored technology for this purpose due to their potential to emulate arbitrary CRNs and known principles to tune their reaction rates. Progress on leakless cascades has demonstrated that DSDs can be arbitrarily robust to spurious "leak" reactions when incorporating systematic domain level redundancy. These improvements in robustness result in slower kinetics of designed reactions. Existing work has demonstrated the kinetic and thermodynamic effects of sequence mismatch introduction and elimination during displacement. We present a systematic, sequence modification strategy for optimizing the kinetics of leakless cascades without practical cost to their robustness. An in-depth case study explores the effects of this optimization when applied to a typical leakless translator cascade. Thermodynamic analysis of energy barriers and kinetic experimental data support that DSD cascades can be fast and robust.
Cite as

Tiernan Kennedy, Cadence Pearce, and Chris Thachuk. Fast and Robust Strand Displacement Cascades via Systematic Design Strategies. In 28th International Conference on DNA Computing and Molecular Programming (DNA 28). Leibniz International Proceedings in Informatics (LIPIcs), Volume 238, pp. 1:1-1:17, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2022)

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@InProceedings{kennedy_et_al:LIPIcs.DNA.28.1,
  author =	{Kennedy, Tiernan and Pearce, Cadence and Thachuk, Chris},
  title =	{{Fast and Robust Strand Displacement Cascades via Systematic Design Strategies}},
  booktitle =	{28th International Conference on DNA Computing and Molecular Programming (DNA 28)},
  pages =	{1:1--1:17},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-253-2},
  ISSN =	{1868-8969},
  year =	{2022},
  volume =	{238},
  editor =	{Ouldridge, Thomas E. and Wickham, Shelley F. J.},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.DNA.28.1},
  URN =		{urn:nbn:de:0030-drops-167869},
  doi =		{10.4230/LIPIcs.DNA.28.1},
  annote =	{Keywords: DNA strand displacement, Energy barriers, Kinetics}
}
Document
DOI: 10.4230/LIPIcs.DNA.27.9
Predicting Minimum Free Energy Structures of Multi-Stranded Nucleic Acid Complexes Is APX-Hard

Authors: Anne Condon, Monir Hajiaghayi, and Chris Thachuk

Published in: LIPIcs, Volume 205, 27th International Conference on DNA Computing and Molecular Programming (DNA 27) (2021)

Abstract
Given multiple nucleic acid strands, what is the minimum free energy (MFE) secondary structure that they can form? As interacting nucleic acid strands are the basis for DNA computing and molecular programming, e.g., in DNA self-assembly and DNA strand displacement systems, determining the MFE structure is an important step in the design and verification of these systems. Efficient dynamic programming algorithms are well known for predicting the MFE pseudoknot-free secondary structure of a single nucleic acid strand. In contrast, we prove that for a simple energy model, the problem of predicting the MFE pseudoknot-free secondary structure formed from multiple interacting nucleic acid strands is NP-hard and also APX-hard. The latter result implies that there does not exist a polynomial time approximation scheme for this problem, unless 𝖯 = NP, and it suggests that heuristic methods should be investigated.
Cite as

Anne Condon, Monir Hajiaghayi, and Chris Thachuk. Predicting Minimum Free Energy Structures of Multi-Stranded Nucleic Acid Complexes Is APX-Hard. In 27th International Conference on DNA Computing and Molecular Programming (DNA 27). Leibniz International Proceedings in Informatics (LIPIcs), Volume 205, pp. 9:1-9:21, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)

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@InProceedings{condon_et_al:LIPIcs.DNA.27.9,
  author =	{Condon, Anne and Hajiaghayi, Monir and Thachuk, Chris},
  title =	{{Predicting Minimum Free Energy Structures of Multi-Stranded Nucleic Acid Complexes Is APX-Hard}},
  booktitle =	{27th International Conference on DNA Computing and Molecular Programming (DNA 27)},
  pages =	{9:1--9:21},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-205-1},
  ISSN =	{1868-8969},
  year =	{2021},
  volume =	{205},
  editor =	{Lakin, Matthew R. and \v{S}ulc, Petr},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.DNA.27.9},
  URN =		{urn:nbn:de:0030-drops-146765},
  doi =		{10.4230/LIPIcs.DNA.27.9},
  annote =	{Keywords: Nucleic Acid Secondary Structure Prediction, APX-Hardness, NP-Hardness}
}
Document
DOI: 10.4230/LIPIcs.DNA.2020.2
Simplifying Chemical Reaction Network Implementations with Two-Stranded DNA Building Blocks

Authors: Robert F. Johnson and Lulu Qian

Published in: LIPIcs, Volume 174, 26th International Conference on DNA Computing and Molecular Programming (DNA 26) (2020)

Abstract
In molecular programming, the Chemical Reaction Network model is often used to describe real or hypothetical systems. Often, an interesting computational task can be done with a known hypothetical Chemical Reaction Network, but often such networks have no known physical implementation. One of the important breakthroughs in the field was that any Chemical Reaction Network can be physically implemented, approximately, using DNA strand displacement mechanisms. This allows us to treat the Chemical Reaction Network model as a programming language and the implementation schemes as its compiler. This also suggests that it would be useful to optimize the result of such a compilation, and in general to find effective ways to design better DNA strand displacement systems. We discuss DNA strand displacement systems in terms of "motifs", short sequences of elementary DNA strand displacement reactions. We argue that describing such motifs in terms of their inputs and outputs, then building larger systems out of the abstracted motifs, can be an efficient way of designing DNA strand displacement systems. We discuss four previously studied motifs in this abstracted way, and present a new motif based on cooperative 4-way strand exchange. We then show how Chemical Reaction Network implementations can be built out of abstracted motifs, discussing existing implementations as well as presenting two new implementations based on 4-way strand exchange, one of which uses the new cooperative motif. The new implementations both have two desirable properties not found in existing implementations, namely both use only at most 2-stranded DNA complexes for signal and fuel complexes and both are physically reversible. There are reasons to believe that those properties may make them more robust and energy-efficient, but at the expense of using more fuel complexes than existing implementation schemes.
Cite as

Robert F. Johnson and Lulu Qian. Simplifying Chemical Reaction Network Implementations with Two-Stranded DNA Building Blocks. In 26th International Conference on DNA Computing and Molecular Programming (DNA 26). Leibniz International Proceedings in Informatics (LIPIcs), Volume 174, pp. 2:1-2:14, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)

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@InProceedings{johnson_et_al:LIPIcs.DNA.2020.2,
  author =	{Johnson, Robert F. and Qian, Lulu},
  title =	{{Simplifying Chemical Reaction Network Implementations with Two-Stranded DNA Building Blocks}},
  booktitle =	{26th International Conference on DNA Computing and Molecular Programming (DNA 26)},
  pages =	{2:1--2:14},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-163-4},
  ISSN =	{1868-8969},
  year =	{2020},
  volume =	{174},
  editor =	{Geary, Cody and Patitz, Matthew J.},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.DNA.2020.2},
  URN =		{urn:nbn:de:0030-drops-129557},
  doi =		{10.4230/LIPIcs.DNA.2020.2},
  annote =	{Keywords: Molecular programming, DNA computing, Chemical Reaction Networks, DNA strand displacement}
}
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