arXiv subjects

David Soloveichik

Publications and source records attributed to David Soloveichik.

At least 19 recordsLinked to original sources

arXiv2026

Scalable Enumeration of Pareto-optimal Polymers for Computing Equilibrium Concentrations

Predicting equilibrium concentrations of molecular complexes is essential for verifying the behavior of engineered DNA systems. However, a finite set of monomer types can in principle generate infinitely many complexes. We study this candidate-enumeration problem in a geometry-free, domain-level abstraction called a domain-monomer system, generalizing Thermodynamic Binding Networks (TBNs) to the unsaturated setting where not every possible bond need be formed. We define Pareto-suboptimal polymers as those that can be split into non-interacting parts, and show that restricting attention to Pareto-optimal polymers is thermodynamically justified: no Pareto-suboptimal polymer appears in any minimum free-energy configuration, and the total equilibrium concentration of such polymers is small. We prove that there are finitely many Pareto-optimal polymers and exactly characterize them via a Hilbert basis computation, extending prior work from the saturated TBN model. To scale this approach to large systems, we develop a framework that restricts the number of different monomer types that a single polymer contains, and uses combinatorial covering designs to reduce the number of Hilbert basis computations required. We benchmark the method on several families of DNA molecular programming systems, demonstrating order-of-magnitude speedups over direct computation while recovering nearly all equilibrium-relevant polymers.

q-bio.BM↗

arXiv2026

Amplification at Equilibrium: Structural and Thermodynamic Limitations, and Implementation

Amplifying weak molecular signals is essential in both natural and engineered biochemical systems. While most amplification schemes operate out of equilibrium, relying on kinetic barriers and fuel-driven cascades, it is also possible to amplify at thermodynamic equilibrium by shifting the energy landscape upon addition of an analyte. Equilibrium amplification is appealing because, in principle, it can remain indefinitely in the untriggered state. In this work, we establish fundamental structural and thermodynamic limits on equilibrium-based amplification. We first prove that dimerization networks--systems restricted to complexes of at most two monomers--are inherently incapable of equilibrium amplification. This no-go theorem explains the absence of amplification in prior undercomplementary "strand commutation" designs. We then show that allowing trimeric complexes breaks this barrier. We propose an isometric trimer-based amplifier whose output preserves the size of the input, enabling modular composition, and validate it experimentally, achieving an amplification factor close to the expected $2\times$. Finally, we derive universal thermodynamic bounds applicable to any equilibrium network regardless of complex size: the maximum amplification factor scales linearly with the free energy of interaction between the analyte and the amplifier components. For nucleic acid systems, this implies that the analyte length must grow linearly with the desired amplification factor, and that composing modular amplifiers yields diminishing returns for a fixed analyte. Together, these results delineate the structural and energetic boundaries of equilibrium amplification and rigorously justify the necessity of out-of-equilibrium approaches for achieving high gain.

q-bio.MN↗

arXiv2025

Computing and Bounding Equilibrium Concentrations in Athermic Chemical Systems

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.

cs.DS↗

arXiv2023

Harvesting Brownian Motion: Zero Energy Computational Sampling

The key factor currently limiting the advancement of computational power of electronic computation is no longer the manufacturing density and speed of components, but rather their high energy consumption. While it has been widely argued that reversible computation can escape the fundamental Landauer limit of $k_B T\ln(2)$ Joules per irreversible computational step, there is disagreement around whether indefinitely reusable computation can be achieved without energy dissipation. Here we focus on the relatively simpler context of sampling problems, which take no input, so avoids modeling the energy costs of the observer perturbing the machine to change its input. Given an algorithm $A$ for generating samples from a distribution, we desire a device that can perpetually generate samples from that distribution driven entirely by Brownian motion. We show that such a device can efficiently execute algorithm $A$ in the sense that we must wait only $O(\text{time}(A)^2)$ between samples. We consider two output models: Las Vegas, which samples from the exact probability distribution every $4$ tries in expectation, and Monte Carlo, in which every try succeeds but the distribution is only approximated. We base our model on continuous-time random walks over the state space graph of a general computational machine, with a space-bounded Turing machine as one instantiation. The problem of sampling a computationally complex probability distribution with no energy dissipation informs our understanding of the energy requirements of computation, and may lead to more energy efficient randomized algorithms.

cs.DS↗

arXiv2023

Thermodynamically Driven Signal Amplification

The field of chemical computation attempts to model computational behavior that arises when molecules, typically nucleic acids, are mixed together. Thermodynamic binding networks (TBNs) is a highly abstracted model that focuses on which molecules are bound to each other in a "thermodynamically stable" sense. Stability is measured based only on how many bonds are formed and how many total complexes are in a configuration, without focusing on how molecules are binding or how they became bound. We study the problem of signal amplification: detecting a small quantity of some molecule and amplifying its signal to something more easily detectable. This problem has natural applications such as disease diagnosis. By focusing on thermodynamically favored outcomes, we seek to design chemical systems that perform the task of signal amplification robustly without relying on kinetic pathways that can be error prone and require highly controlled conditions (e.g., PCR amplification). It might appear that a small change in concentrations can result in only small changes to the thermodynamic equilibrium of a molecular system. However, we show that it is possible to design a TBN that can "exponentially amplify" a signal represented by a single copy of a monomer called the analyte: this TBN has exactly one stable state before adding the analyte and exactly one stable state afterward, and those two states "look very different" from each other. We also show a corresponding negative result: a doubly exponential upper bound, meaning that there is no TBN that can amplify a signal by an amount more than doubly exponential in the number and sizes of different molecules that comprise it. Our work informs the fundamental question of how a thermodynamic equilibrium can change as a result of a small change to the system (adding a single molecule copy).

cs.ET↗

arXiv2023

Optimal Information Encoding in Chemical Reaction Networks

Discrete chemical reaction networks formalize the interactions of molecular species in a well-mixed solution as stochastic events. Given their basic mathematical and physical role, the computational power of chemical reaction networks has been widely studied in the molecular programming and distributed computing communities. While for Turing-universal systems there is a universal measure of optimal information encoding based on Kolmogorov complexity, chemical reaction networks are not Turing universal unless error and unbounded molecular counts are permitted. Nonetheless, here we show that the optimal number of reactions to generate a specific count $x \in \mathbb{N}$ with probability $1$ is asymptotically equal to a ``space-aware'' version of the Kolmogorov complexity of $x$, defined as $\mathrm{\widetilde{K}s}(x) = \min_p\left\{\lvert p \rvert / \log \lvert p \rvert + \log(\texttt{space}(\mathcal{U}(p))) : \mathcal{U}(p) = x \right\}$, where $p$ is a program for universal Turing machine $\mathcal{U}$. This version of Kolmogorov complexity incorporates not just the length of the shortest program for generating $x$, but also the space usage of that program. Probability $1$ computation is captured by the standard notion of stable computation from distributed computing, but we limit our consideration to chemical reaction networks obeying a stronger constraint: they ``know when they are done'' in the sense that they produce a special species to indicate completion. As part of our results, we develop a module for encoding and unpacking any $b$ bits of information via $O(b/\log{b})$ reactions, which is information-theoretically optimal for incompressible information. Our work provides one answer to the question of how succinctly chemical self-organization can be encoded -- in the sense of generating precise molecular counts of species as the desired state.

cs.CC↗

arXiv2023

Rate-Independent Computation in Continuous Chemical Reaction Networks

Coupled chemical interactions in a well-mixed solution are commonly formalized as chemical reaction networks (CRNs). However, despite the widespread use of CRNs in the natural sciences, the range of computational behaviors exhibited by CRNs is not well understood. Here we study the following problem: what functions $f:\mathbb{R}^k \to \mathbb{R}$ can be computed by a CRN, in which the CRN eventually produces the correct amount of the "output" molecule, no matter the rate at which reactions proceed? This captures a previously unexplored, but very natural class of computations: for example, the reaction $X_1 + X_2 \to Y$ can be thought to compute the function $y = \min(x_1, x_2)$. Such a CRN is robust in the sense that it is correct no matter the kinetic model of chemistry, so long as it respects the stoichiometric constraints. We develop a reachability relation based on "what could happen" if reaction rates can vary arbitrarily over time. We define *stable computation* analogously to probability 1 computation in distributed computing, and connect it with a seemingly stronger notion of rate-independent computation based on convergence under a wide class of generalized rate laws. We also consider the "dual-rail representation" that can represent negative values as the difference of two concentrations and allows the composition of CRN modules. We prove that a function is rate-independently computable if and only if it is piecewise linear (with rational coefficients) and continuous (dual-rail representation), or non-negative with discontinuities occurring only when some inputs switch from zero to positive (direct representation). The many contexts where continuous piecewise linear functions are powerful targets for implementation, combined with the systematic construction we develop for computing these functions, demonstrate the potential of rate-independent chemical computation.

cs.ET↗

arXiv2021

Tight Bounds on the Spooky Pebble Game: Recycling Qubits with Measurements

Pebble games are popular models for analyzing time-space trade-offs. In particular, the reversible pebble game is often applied in quantum algorithms like Grover's search to efficiently simulate classical computation on inputs in superposition. However, the reversible pebble game cannot harness the additional computational power granted by irreversible intermediate measurements. The spooky pebble game, which models interleaved measurements and adaptive phase corrections, reduces the number of qubits beyond what reversible approaches can achieve. While the spooky pebble game does not reduce the total space (bits plus qubits) complexity of the simulation, it reduces the amount of space that must be stored in qubits. We prove asymptotically tight trade-offs for the spooky pebble game on a line with any pebble bound, giving a tight time-qubit tradeoff for simulating arbitrary classical sequential computation with the spooky pebble game. For example, for all $\epsilon \in (0,1]$, any classical computation requiring time $T$ and space $S$ can be implemented on a quantum computer using only $O(T/ \epsilon)$ gates and $O(T^{\epsilon}S^{1-\epsilon})$ qubits. This improves on the best known bound for the reversible pebble game with that number of qubits, which uses $O(2^{1/\epsilon} T)$ gates. We also consider the spooky pebble game on more general directed acyclic graphs (DAGs), capturing fine-grained data dependency in computation. We show that for an arbitrary DAG even approximating the number of required pebbles in the spooky pebble game is PSPACE-hard. Despite this, we are able to construct a time-efficient strategy for pebbling binary trees that uses the minimum number of pebbles.

quant-ph↗

arXiv2021

Programming and Training Rate-Independent Chemical Reaction Networks

Embedding computation in biochemical environments incompatible with traditional electronics is expected to have wide-ranging impact in synthetic biology, medicine, nanofabrication and other fields. Natural biochemical systems are typically modeled by chemical reaction networks (CRNs), and CRNs can be used as a specification language for synthetic chemical computation. In this paper, we identify a class of CRNs called non-competitive (NC) whose equilibria are absolutely robust to reaction rates and kinetic rate law, because their behavior is captured solely by their stoichiometric structure. Unlike prior work on rate-independent CRNs, checking non-competition and using it as a design criterion is easy and promises robust output. We also present a technique to program NC-CRNs using well-founded deep learning methods, showing a translation procedure from rectified linear unit (ReLU) neural networks to NC-CRNs. In the case of binary weight ReLU networks, our translation procedure is surprisingly tight in the sense that a single bimolecular reaction corresponds to a single ReLU node and vice versa. This compactness argues that neural networks may be a fitting paradigm for programming rate-independent chemical computation. As proof of principle, we demonstrate our scheme with numerical simulations of CRNs translated from neural networks trained on traditional machine learning datasets (IRIS and MNIST), as well as tasks better aligned with potential biological applications including virus detection and spatial pattern formation.

cs.LG↗

arXiv2020

Composable Rate-Independent Computation in Continuous Chemical Reaction Networks

Biological regulatory networks depend upon chemical interactions to process information. Engineering such molecular computing systems is a major challenge for synthetic biology and related fields. The chemical reaction network (CRN) model idealizes chemical interactions, allowing rigorous reasoning about the computational power of chemical kinetics. Here we focus on function computation with CRNs, where we think of the initial concentrations of some species as the input and the equilibrium concentration of another species as the output. Specifically, we are concerned with CRNs that are rate-independent (the computation must be correct independent of the reaction rate law) and composable ($f\circ g$ can be computed by concatenating the CRNs computing $f$ and $g$). Rate independence and composability are important engineering desiderata, permitting implementations that violate mass-action kinetics, or even "well-mixedness", and allowing the systematic construction of complex computation via modular design. We show that to construct composable rate-independent CRNs, it is necessary and sufficient to ensure that the output species of a module is not a reactant in any reaction within the module. We then exactly characterize the functions computable by such CRNs as superadditive, positive-continuous, and piecewise rational linear. Thus composability severely limits rate-independent computation unless more sophisticated input/output encodings are used.

cs.ET↗

arXiv2020

CRNs Exposed: Systematic Exploration of Chemical Reaction Networks

Formal methods have enabled breakthroughs in many fields, such as in hardware verification, machine learning and biological systems. The key object of interest in systems biology, synthetic biology, and molecular programming is chemical reaction networks (CRNs) which formalizes coupled chemical reactions in a well-mixed solution. CRNs are pivotal for our understanding of biological regulatory and metabolic networks, as well as for programming engineered molecular behavior. Although it is clear that small CRNs are capable of complex dynamics and computational behavior, it remains difficult to explore the space of CRNs in search for desired functionality. We use Alloy, a tool for expressing structural constraints and behavior in software systems, to enumerate CRNs with declaratively specified properties. We show how this framework can enumerate CRNs with a variety of structural constraints including biologically motivated catalytic networks and metabolic networks, and seesaw networks motivated by DNA nanotechnology. We also use the framework to explore analog function computation in rate-independent CRNs. By computing the desired output value with stoichiometry rather than with reaction rates (in the sense that $X \to Y+Y$ computes multiplication by $2$), such CRNs are completely robust to the choice of reaction rates or rate law. We find the smallest CRNs computing the max, minmax, abs and ReLU (rectified linear unit) functions in a natural subclass of rate-independent CRNs where rate-independence follows from structural network properties.

cs.ET↗

arXiv2020

Deep Molecular Programming: A Natural Implementation of Binary-Weight ReLU Neural Networks

Embedding computation in molecular contexts incompatible with traditional electronics is expected to have wide ranging impact in synthetic biology, medicine, nanofabrication and other fields. A key remaining challenge lies in developing programming paradigms for molecular computation that are well-aligned with the underlying chemical hardware and do not attempt to shoehorn ill-fitting electronics paradigms. We discover a surprisingly tight connection between a popular class of neural networks (binary-weight ReLU aka BinaryConnect) and a class of coupled chemical reactions that are absolutely robust to reaction rates. The robustness of rate-independent chemical computation makes it a promising target for bioengineering implementation. We show how a BinaryConnect neural network trained in silico using well-founded deep learning optimization techniques, can be compiled to an equivalent chemical reaction network, providing a novel molecular programming paradigm. We illustrate such translation on the paradigmatic IRIS and MNIST datasets. Toward intended applications of chemical computation, we further use our method to generate a chemical reaction network that can discriminate between different virus types based on gene expression levels. Our work sets the stage for rich knowledge transfer between neural network and molecular programming communities.

cs.NE↗

arXiv2020

Programming Substrate-Independent Kinetic Barriers with Thermodynamic Binding Networks

Engineering molecular systems that exhibit complex behavior requires the design of kinetic barriers. For example, an effective catalytic pathway must have a large barrier when the catalyst is absent. While programming such energy barriers seems to require knowledge of the specific molecular substrate, we develop a novel substrate-independent approach. We extend the recently-developed model known as thermodynamic binding networks, demonstrating programmable kinetic barriers that arise solely from the thermodynamic driving forces of bond formation and the configurational entropy of forming separate complexes. Our kinetic model makes relatively weak assumptions, which implies that energy barriers predicted by our model would exist in a wide variety of systems and conditions. We demonstrate that our model is robust by showing that several variations in its definition result in equivalent energy barriers. We apply this model to design catalytic systems with an arbitrarily large energy barrier to uncatalyzed reactions. Our results could yield robust amplifiers using DNA strand displacement, a popular technology for engineering synthetic reaction pathways, and suggest design strategies for preventing undesired kinetic behavior in a variety of molecular systems.

cs.ET↗

arXiv2019

Robust Detection in Leak-Prone Population Protocols

In contrast to electronic computation, chemical computation is noisy and susceptible to a variety of sources of error, which has prevented the construction of robust complex systems. To be effective, chemical algorithms must be designed with an appropriate error model in mind. Here we consider the model of chemical reaction networks that preserve molecular count (population protocols), and ask whether computation can be made robust to a natural model of unintended "leak" reactions. Our definition of leak is motivated by both the particular spurious behavior seen when implementing chemical reaction networks with DNA strand displacement cascades, as well as the unavoidable side reactions in any implementation due to the basic laws of chemistry. We develop a new "Robust Detection" algorithm for the problem of fast (logarithmic time) single molecule detection, and prove that it is robust to this general model of leaks. Besides potential applications in single molecule detection, the error-correction ideas developed here might enable a new class of robust-by-design chemical algorithms. Our analysis is based on a non-standard hybrid argument, combining ideas from discrete analysis of population protocols with classic Markov chain techniques.

cs.DS↗

arXiv2019

CRN++: Molecular Programming Language

Synthetic biology is a rapidly emerging research area, with expected wide-ranging impact in biology, nanofabrication, and medicine. A key technical challenge lies in embedding computation in molecular contexts where electronic micro-controllers cannot be inserted. This necessitates effective representation of computation using molecular components. While previous work established the Turing-completeness of chemical reactions, defining representations that are faithful, efficient, and practical remains challenging. This paper introduces CRN++, a new language for programming deterministic (mass-action) chemical kinetics to perform computation. We present its syntax and semantics, and build a compiler translating CRN++ programs into chemical reactions, thereby laying the foundation of a comprehensive framework for molecular programming. Our language addresses the key challenge of embedding familiar imperative constructs into a set of chemical reactions happening simultaneously and manipulating real-valued concentrations. Although some deviation from ideal output value cannot be avoided, we develop methods to minimize the error, and implement error analysis tools. We demonstrate the feasibility of using CRN++ on a suite of well-known algorithms for discrete and real-valued computation. CRN++ can be easily extended to support new commands or chemical reaction implementations, and thus provides a foundation for developing more robust and practical molecular programs.

cs.ET↗

arXiv2019

Computing properties of stable configurations of thermodynamic binding networks

The promise of chemical computation lies in controlling systems incompatible with traditional electronic micro-controllers, with applications in synthetic biology and nano-scale manufacturing. Computation is typically embedded in kinetics---the specific time evolution of a chemical system. However, if the desired output is not thermodynamically stable, basic physical chemistry dictates that thermodynamic forces will drive the system toward error throughout the computation. The thermodynamic binding network (TBN) model was introduced to formally study how the thermodynamic equilibrium can be made consistent with the desired computation, and it idealizes tradeoffs between configurational entropy and binding. Here we prove the computational hardness of natural questions about TBNs and develop a practical algorithm for verifying the correctness of constructions by translating the problem into propositional logic and solving the resulting formula. The TBN model together with automated verification tools will help inform strategies for error reduction in molecular computing, including the extensively studied models of strand displacement cascades and algorithmic tile assembly.

cs.ET↗

arXiv2018

Hardness of computing and approximating predicates and functions with leaderless population protocols

Population protocols are a distributed computing model appropriate for describing massive numbers of agents with limited computational power. A population protocol "has an initial leader" if every valid initial configuration contains a single agent in a special "leader" state that helps to coordinate the computation. Although the class of predicates and functions computable with probability 1 is the same whether or not there is an initial leader (semilinear functions and predicates), it is not known whether a leader is necessary for fast computation. Efficient population protocols are generally defined as those computing in polylogarithmic in $n$ (parallel) time. We consider leaderless population protocols, regarding the computation finished when a configuration is reached from which a different output is no longer reachable. In this setting we show that a wide class of functions and predicates computable by population protocols are not efficiently computable (they require at least linear time to stabilize on a correct answer), nor are some linear functions even efficiently approximable. For example, the widely studied parity, majority, and equality predicates cannot be computed in sublinear time. Moreover, it requires at least linear time for a population protocol even to approximate any linear function with a coefficient outside of $\mathbb{N}$: for sufficiently small $γ> 0$, the output of a sublinear time protocol can stabilize outside the interval $f(m) (1 \pm γ)$ on infinitely many inputs $m$. We also show that it requires linear time to exactly compute a wide range of semilinear functions (e.g., $f(m)=m$ if $m$ is even and $2m$ if $m$ is odd). Finally, we show that with a sufficiently large value of $γ$, a population protocol can approximate any linear $f$ with nonnegative rational coefficients, within approximation factor $γ$, in $O(\log n)$ time.

cs.DC↗

arXiv2017

Thermodynamic Binding Networks

Strand displacement and tile assembly systems are designed to follow prescribed kinetic rules (i.e., exhibit a specific time-evolution). However, the expected behavior in the limit of infinite time--known as thermodynamic equilibrium--is often incompatible with the desired computation. Basic physical chemistry implicates this inconsistency as a source of unavoidable error. Can the thermodynamic equilibrium be made consistent with the desired computational pathway? In order to formally study this question, we introduce a new model of molecular computing in which computation is driven by the thermodynamic driving forces of enthalpy and entropy. To ensure greatest generality we do not assume that there are any constraints imposed by geometry and treat monomers as unstructured collections of binding sites. In this model we design Boolean AND/OR formulas, as well as a self-assembling binary counter, where the thermodynamically favored states are exactly the desired final output configurations. Though inspired by DNA nanotechnology, the model is sufficiently general to apply to a wide variety of chemical systems.

cs.ET↗