Improved computation of natural logarithm using chemical reaction networks

Recent researches have focused on nucleic acids as a substrate for designing biomolecular circuits for in situ monitoring and control. A common approach is to express them by a set of idealised abstract chemical reaction networks (ACRNs). Here, we present new results on how abstract chemical reactions, viz., catalysis, annihilation and degradation, can be used to implement circuit that accurately computes logarithm function using the method of Cubic Arithmetic-Geometric Mean (AGM)

Conceptual Design of RNA-RNA Interaction Based Devices

AbstractA key goal of synthetic biology is to use biological molecules to create novel biological systems. Due to their role as transmitters in such systems, RNA molecules have gained much attention from synthetic biologists to design and construct novel RNA molecules with desirable functions and properties. In recent decades, the design of RNAs, however, has been limited to RNA architecture with primitive functions: aptamer and catalysis. To expand the paradigm of RNA-based design, we herein propose a conceptual design of RNA-RNA interaction based systems, considering domain-based structures of RNAs, as well as thermodynamic properties of RNA molecules and their interactions. Two evaluation scores, namely structural score (SS) and affinity score (AS), are used as criteria for selection of proper RNA sets. We employ this concept to design various RNA sets, each of which contains three RNA strands that altogether function like a comparator device. With these criteria, we show that four out of forty RNA sets would behave like a biological comparator since they have appropriate structure (SS=1) and proper interaction order (AS>1). The proposed scores are proven to be proper criteria for selection of RNA sets with required functions. This preliminary design offers an opportunity for synthetic biologists to expand the design of RNA sequence from a single strand to multiple strands that would behave in the same manner as enzymatic reactions

Implementing nonlinear feedback controllers using DNA strand displacement reactions

We show how an important class of nonlinear feedback controllers can be designed using idealized abstract chemical reactions and implemented via DNA strand displacement (DSD) reactions. Exploiting chemical reaction networks (CRNs) as a programming language for the design of complex circuits and networks, we show how a set of unimolecular and bimolecular reactions can be used to realize input-output dynamics that produce a nonlinear quasi sliding mode (QSM) feedback controller. The kinetics of the required chemical reactions can then be implemented as enzyme-free, enthalpy/entropy driven DNA reactions using a toehold mediated strand displacement mechanism via Watson-Crick base pairing and branch migration. We demonstrate that the closed loop response of the nonlinear QSM controller outperforms a traditional linear controller by facilitating much faster tracking response dynamics without introducing overshoots in the transient response. The resulting controller is highly modular and is less affected by retroactivity effects than standard linear designs

Effective design principles for leakless strand displacement systems

Artificially designed molecular systems with programmable behaviors have become a valuable tool in chemistry, biology, material science, and medicine. Although information processing in biological regulatory pathways is remarkably robust to error, it remains a challenge to design molecular systems that are similarly robust. With functionality determined entirely by secondary structure of DNA, strand displacement has emerged as a uniquely versatile building block for cell-free biochemical networks. Here, we experimentally investigate a design principle to reduce undesired triggering in the absence of input (leak), a side reaction that critically reduces sensitivity and disrupts the behavior of strand displacement cascades. Inspired by error correction methods exploiting redundancy in electrical engineering, we ensure a higher-energy penalty to leak via logical redundancy. Our design strategy is, in principle, capable of reducing leak to arbitrarily low levels, and we experimentally test two levels of leak reduction for a core “translator” component that converts a signal of one sequence into that of another. We show that the leak was not measurable in the high-redundancy scheme, even for concentrations that are up to 100 times larger than typical. Beyond a single translator, we constructed a fast and low-leak translator cascade of nine strand displacement steps and a logic OR gate circuit consisting of 10 translators, showing that our design principle can be used to effectively reduce leak in more complex chemical systems

SPIDER-WEB enables stable, repairable, and encryptible algorithms under arbitrary local biochemical constraints in DNA-based storage

DNA has been considered as a promising medium for storing digital information. Despite the biochemical progress in DNA synthesis and sequencing, novel coding algorithms need to be constructed under the specific constraints in DNA-based storage. Many functional operations and storage carriers were introduced in recent years, bringing in various biochemical constraints including but not confined to long single-nucleotide repeats and abnormal GC content. Existing coding algorithms are not applicable or unstable due to more local biochemical constraints and their combinations. In this paper, we design a graph-based architecture, named SPIDER-WEB, to generate corresponding graph-based algorithms under arbitrary local biochemical constraints. These generated coding algorithms could be used to encode arbitrary digital data as DNA sequences directly or served as a benchmark for the follow-up construction of coding algorithms. To further consider recovery and security issues existing in the storage field, it also provides pluggable algorithmic patches based on the generated coding algorithms: path-based correcting and mapping shuffling. They provide approaches for probabilistic error correction and symmetric encryption respectively.Comment: 30 pages; 12 figures; 2 table

Integrating DNA strand-displacement circuitry with DNA tile self-assembly

DNA nanotechnology has emerged as a reliable and programmable way of controlling matter at the nanoscale through the specificity of Watson–Crick base pairing, allowing both complex self-assembled structures with nanometer precision and complex reaction networks implementing digital and analog behaviors. Here we show how two well-developed frameworks, DNA tile self-assembly and DNA strand-displacement circuits, can be systematically integrated to provide programmable kinetic control of self-assembly. We demonstrate the triggered and catalytic isothermal self-assembly of DNA nanotubes over 10 µm long from precursor DNA double-crossover tiles activated by an upstream DNA catalyst network. Integrating more sophisticated control circuits and tile systems could enable precise spatial and temporal organization of dynamic molecular structures

A domain-level DNA strand displacement reaction enumerator allowing arbitrary non-pseudoknotted secondary structures

Information technologies enable programmers and engineers to design and synthesize systems of startling complexity that nonetheless behave as intended. This mastery of complexity is made possible by a hierarchy of formal abstractions that span from high-level programming languages down to low-level implementation specifications, with rigorous connections between the levels. DNA nanotechnology presents us with a new molecular information technology whose potential has not yet been fully unlocked in this way. Developing an effective hierarchy of abstractions may be critical for increasing the complexity of programmable DNA systems. Here, we build on prior practice to provide a new formalization of ‘domain-level’ representations of DNA strand displacement systems that has a natural connection to nucleic acid biophysics while still being suitable for formal analysis. Enumeration of unimolecular and bimolecular reactions provides a semantics for programmable molecular interactions, with kinetics given by an approximate biophysical model. Reaction condensation provides a tractable simplification of the detailed reactions that respects overall kinetic properties. The applicability and accuracy of the model is evaluated across a wide range of engineered DNA strand displacement systems. Thus, our work can serve as an interface between lower-level DNA models that operate at the nucleotide sequence level, and high-level chemical reaction network models that operate at the level of interactions between abstract species

Design and synthesis of dynamically assembling DNA nanostructures

Kinetically controlled isothermal growth is fundamental to biological development, but it remains challenging to rationally design molecular systems that self-assemble isothermally into complex geometries via prescribed assembly and disassembly pathways. By exploiting the programmable chemistry of base pairing, sophisticated spatial and temporal control have both been demonstrated in DNA self-assembly, but largely as separate pursuits. This dissertation extends a new approach, called developmental self-assembly, that integrates temporal with spatial control by using a prescriptive molecular program to specify the kinetic pathways by which DNA molecules isothermally self-assemble into well-defined three-dimensional geometries.Chemistry and Chemical Biolog