Affiliation:
1. California Institute of Technology, Pasadena, CA, USA
Abstract
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.
Funder
Gordon and Betty Moore Foundation
National Science Foundation
Subject
Biomedical Engineering,Biochemistry,Biomaterials,Bioengineering,Biophysics,Biotechnology
Cited by
12 articles.
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