A polymer model of bacterial supercoiled DNA including structural transitions of the double helix

DNA supercoiling, the under or overwinding of DNA, is a key physical mechanism both participating to compaction of bacterial genomes and making genomic sequences adopt various structural forms. DNA supercoiling may lead to the formation of braided superstructures (plectonemes), or it may locally destabilize canonical B-DNA to generate denaturation bubbles, left-handed Z-DNA and other functional alternative forms. Prediction of the relative fraction of these structures has been limited because of a lack of predictive polymer models that can capture the multiscale properties of long DNA molecules. In this work, we address this issue by extending the self-avoiding rod-like chain model of DNA so that every site of the chain is allocated with an additional structural degree of freedom reflecting variations of DNA forms. Efficient simulations of the model reveal its relevancy to capture multiscale properties of long chains (here up to 21 kb) as reported in magnetic tweezers experiments. Well-controlled approximations further lead to accurate analytical estimations of thermodynamic properties in the high force regime, providing, in combination with experiments, a simple, yet powerful framework to infer physical parameters describing alternative forms. In this regard, using simulated data, we find that extension curves at forces above 2 pN may lead, alone, to erroneous parameter estimations as a consequence of an underdetermination problem. We thus revisit published data in light of these findings and discuss the relevancy of previously proposed sets of parameters for both denatured and left-handed DNA forms. Altogether, our work paves the way for a scalable quantitative model of bacterial DNA.