title: Modeling DNA thermodynamics under torsional stress.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology, University of Texas Medical Branch, Galveston, Texas. Electronic address: mpettitt@utmb.edu.
authors.forename: B Montgomery
authors.initials: BM
authors.lastname: Pettitt
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D009994:Osmolar Concentration; D012399:Rotation; D013314:Stress, Mechanical; D013696:Temperature; D013816:Thermodynamics
chemical_list: D004247:DNA