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2017 | OriginalPaper | Chapter

Inferring Parameters for an Elementary Step Model of DNA Structure Kinetics with Locally Context-Dependent Arrhenius Rates

Authors: Sedigheh Zolaktaf, Frits Dannenberg, Xander Rudelis, Anne Condon, Joseph M. Schaeffer, Mark Schmidt, Chris Thachuk, Erik Winfree

Published in: DNA Computing and Molecular Programming

Publisher: Springer International Publishing

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Abstract

Models of nucleic acid thermal stability are calibrated to a wide range of experimental observations, and typically predict equilibrium probabilities of nucleic acid secondary structures with reasonable accuracy. By comparison, a similar calibration and evaluation of nucleic acid kinetic models to a broad range of measurements has not been attempted so far. We introduce an Arrhenius model of interacting nucleic acid kinetics that relates the activation energy of a state transition with the immediate local environment of the affected base pair. Our model can be used in stochastic simulations to estimate kinetic properties and is consistent with existing thermodynamic models. We infer parameters for our model using an ensemble Markov chain Monte Carlo (MCMC) approach on a training dataset with 320 kinetic measurements of hairpin closing and opening, helix association and dissociation, bubble closing and toehold-mediated strand exchange. Our new model surpasses the performance of the previously established Metropolis model both on the training set and on a testing set of size 56 composed of toehold-mediated 3-way strand displacement with mismatches and hairpin opening and closing rates: reaction rates are predicted to within a factor of three for \(93.4\%\) and \(78.5\%\) of reactions for the training and testing sets, respectively.
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Metadata
Title
Inferring Parameters for an Elementary Step Model of DNA Structure Kinetics with Locally Context-Dependent Arrhenius Rates
Authors
Sedigheh Zolaktaf
Frits Dannenberg
Xander Rudelis
Anne Condon
Joseph M. Schaeffer
Mark Schmidt
Chris Thachuk
Erik Winfree
Copyright Year
2017
DOI
https://doi.org/10.1007/978-3-319-66799-7_12