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Automated sequence-level analysis of kinetics and thermodynamics for domain-level DNA strand-displacement systems

As an engineering material, DNA is well suited for the construction of biochemical circuits and systems, because it is simple enough that its interactions can be rationally designed using Watson–Crick base pairing rules, yet the design space is remarkably rich. When designing DNA systems, this simpl...

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Autores principales: Berleant, Joseph, Berlind, Christopher, Badelt, Stefan, Dannenberg, Frits, Schaeffer, Joseph, Winfree, Erik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303802/
https://www.ncbi.nlm.nih.gov/pubmed/30958232
http://dx.doi.org/10.1098/rsif.2018.0107
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author Berleant, Joseph
Berlind, Christopher
Badelt, Stefan
Dannenberg, Frits
Schaeffer, Joseph
Winfree, Erik
author_facet Berleant, Joseph
Berlind, Christopher
Badelt, Stefan
Dannenberg, Frits
Schaeffer, Joseph
Winfree, Erik
author_sort Berleant, Joseph
collection PubMed
description As an engineering material, DNA is well suited for the construction of biochemical circuits and systems, because it is simple enough that its interactions can be rationally designed using Watson–Crick base pairing rules, yet the design space is remarkably rich. When designing DNA systems, this simplicity permits using functional sections of each strand, called domains, without considering particular nucleotide sequences. However, the actual sequences used may have interactions not predicted at the domain-level abstraction, and new rigorous analysis techniques are needed to determine the extent to which the chosen sequences conform to the system’s domain-level description. We have developed a computational method for verifying sequence-level systems by identifying discrepancies between the domain-level and sequence-level behaviour. This method takes a DNA system, as specified using the domain-level tool Peppercorn, and analyses data from the stochastic sequence-level simulator Multistrand and sequence-level thermodynamic analysis tool NUPACK to estimate important aspects of the system, such as reaction rate constants and secondary structure formation. These techniques, implemented as the Python package KinDA, will allow researchers to predict the kinetic and thermodynamic behaviour of domain-level systems after sequence assignment, as well as to detect violations of the intended behaviour.
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spelling pubmed-63038022018-12-26 Automated sequence-level analysis of kinetics and thermodynamics for domain-level DNA strand-displacement systems Berleant, Joseph Berlind, Christopher Badelt, Stefan Dannenberg, Frits Schaeffer, Joseph Winfree, Erik J R Soc Interface Life Sciences–Mathematics interface As an engineering material, DNA is well suited for the construction of biochemical circuits and systems, because it is simple enough that its interactions can be rationally designed using Watson–Crick base pairing rules, yet the design space is remarkably rich. When designing DNA systems, this simplicity permits using functional sections of each strand, called domains, without considering particular nucleotide sequences. However, the actual sequences used may have interactions not predicted at the domain-level abstraction, and new rigorous analysis techniques are needed to determine the extent to which the chosen sequences conform to the system’s domain-level description. We have developed a computational method for verifying sequence-level systems by identifying discrepancies between the domain-level and sequence-level behaviour. This method takes a DNA system, as specified using the domain-level tool Peppercorn, and analyses data from the stochastic sequence-level simulator Multistrand and sequence-level thermodynamic analysis tool NUPACK to estimate important aspects of the system, such as reaction rate constants and secondary structure formation. These techniques, implemented as the Python package KinDA, will allow researchers to predict the kinetic and thermodynamic behaviour of domain-level systems after sequence assignment, as well as to detect violations of the intended behaviour. The Royal Society 2018-12 2018-12-19 /pmc/articles/PMC6303802/ /pubmed/30958232 http://dx.doi.org/10.1098/rsif.2018.0107 Text en © 2018 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Life Sciences–Mathematics interface
Berleant, Joseph
Berlind, Christopher
Badelt, Stefan
Dannenberg, Frits
Schaeffer, Joseph
Winfree, Erik
Automated sequence-level analysis of kinetics and thermodynamics for domain-level DNA strand-displacement systems
title Automated sequence-level analysis of kinetics and thermodynamics for domain-level DNA strand-displacement systems
title_full Automated sequence-level analysis of kinetics and thermodynamics for domain-level DNA strand-displacement systems
title_fullStr Automated sequence-level analysis of kinetics and thermodynamics for domain-level DNA strand-displacement systems
title_full_unstemmed Automated sequence-level analysis of kinetics and thermodynamics for domain-level DNA strand-displacement systems
title_short Automated sequence-level analysis of kinetics and thermodynamics for domain-level DNA strand-displacement systems
title_sort automated sequence-level analysis of kinetics and thermodynamics for domain-level dna strand-displacement systems
topic Life Sciences–Mathematics interface
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303802/
https://www.ncbi.nlm.nih.gov/pubmed/30958232
http://dx.doi.org/10.1098/rsif.2018.0107
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