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

View Researcher II's Other Codes

Disclaimer: The provided code links for this paper are external links. Science Nest has no responsibility for the accuracy, legality or content of these links. Also, by downloading this code(s), you agree to comply with the terms of use as set out by the author(s) of the code(s).

Authors Sedigheh Zolaktaf, Frits Dannenberg, +5 authors Erik Winfree
Journal/Conference Name DNA
Paper Category
Paper 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.
Date of publication 2017
Code Programming Language Python
Comment

Copyright Researcher II 2021