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

Abstract

<jats:p>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.</jats:p>

Automated exploration of DNA-based structure self-assembly networks

“…A domain is a short sequence of nucleotides that is used as a shorthand in representing strands. Domains are simply represented as a single letter, potentially followed by a* to represent a complementary sequence (kernel notation [ 22 ]). Furthermore, independent domains are considered orthogonal, meaning that they do not interact with each other.…”

“…We use Peppercorn, an enumerator for DNA strand displacement reactions developed by Badelt et al [ 22 ]. Peppercorn computes all possible domain-level interactions and pathways among a given set of starting DNA structures, with newly found structures added to the working set.…”

“…As such, we rely instead on the MAP-Elites algorithm [ 21 ], which is capable of exploring large search space efficiently. We combine it with the Peppercorn DNA reaction enumerator [ 22 ] to extract the features of each tested CRN. Sets of strands that are expected to produce a wide range of structures are then evaluated with NUPACK [ 23 ].…”

Verifying polymer reaction networks using bisimulation

“…Similarly, the minimal states for λ i w i x i + Q i → λ i w i + x f i are either λ i w i x + i by itself, or one of λ i w i x i , λ i w i x i 0 − i , or λ i w i x i 1 − i plus one of any non-λ i w i x + i species providing Q i . These states implement the formal reaction as follows: any species providing Q i releases the implementation Q i by a reaction of type (3) or (5) as appropriate; any 0 − i or 1 − i "falls off" by a reverse reaction of type (1); free Q i joins λ i by a reverse reaction of type (5) or λ i w i x i by a reverse reaction of type (3); and finally the formal reaction is implemented by a reverse reaction of type ( 2) or (4) as appropriate.…”

BioCRNpyler: Compiling Chemical Reaction Networks from Biomolecular Parts in Diverse Contexts

“…As the name would suggest, BioCRNpyler (pronounced bio-compiler) is a Python package that compiles CRNs from simple specifications of biological motifs and contexts. This package is inspired by the molecular compilers developed by the DNA-strand displacement community and molecular programming communities which, broadly speaking, aim to compile models of DNA circuit implementations from simpler CRN specifications 11–13 or rudimentary programming languages. 14,15 However, BioCRNpyler differs from these tools for three main reasons: first, it is not focused only on DNA implementations of chemical computation; second, it does not take the form of a traditional programming language; and third, modeling assumptions and compilation schemas can be easily redefined by the user.…”