Modeling DNA thermodynamics under torsional stress

Qian Wang, Bernard Pettitt

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Negatively twisted DNA is essential to many biological functions. Due to torsional stress, duplex DNA can have local, sequence-dependent structural defects. In this work, a thermodynamic model of DNA was built to qualitatively predict the local sequence-dependent mechanical instabilities under torsional stress. The results were compared to both simulation of a coarse-grained model and experiment results. By using the Kirkwood superposition approximation, we built an analytical model to represent the free energy difference ΔW of a hydrogen-bonded basepair between the B-form helical state and the basepair opened (or locally melted) state, within a given sequence under torsional stress. We showed that ΔW can be well approximated by two-body interactions with its nearest-sequence-neighbor basepairs plus a free energy correction due to long-range correlations. This model is capable of rapidly predicting the position and thermodynamics of local defects in a given sequence. The result qualitatively matches with an in vitro experiment for a long DNA sequence (>4000 basepairs). The 12 parameters used in this model can be further quantitatively refined when more experimental data are available.

Original languageEnglish (US)
Pages (from-to)1182-1193
Number of pages12
JournalBiophysical Journal
Volume106
Issue number5
DOIs
StatePublished - Mar 4 2014

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Thermodynamics
DNA
Hydrogen

ASJC Scopus subject areas

  • Biophysics

Cite this

Modeling DNA thermodynamics under torsional stress. / Wang, Qian; Pettitt, Bernard.

In: Biophysical Journal, Vol. 106, No. 5, 04.03.2014, p. 1182-1193.

Research output: Contribution to journalArticle

Wang, Qian ; Pettitt, Bernard. / Modeling DNA thermodynamics under torsional stress. In: Biophysical Journal. 2014 ; Vol. 106, No. 5. pp. 1182-1193.
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