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Probing the microscopic flexibility of DNA from melting temperatures

Abstract

The microscopic flexibility of DNA is a key ingredient for understanding its interaction with proteins and drugs but is still poorly understood and technically challenging to measure. Several experimental methods probe very long DNA samples, but these miss local flexibility details. Others mechanically disturb or modify short molecules and therefore do not obtain flexibility properties of unperturbed and pristine DNA. Here, we show that it is possible to extract very detailed flexibility information about unmodified DNA from melting temperatures with statistical physics models. We were able to retrieve, from published melting temperatures, several established flexibility properties such as the presence of highly flexible TATA regions of genomic DNA and support recent findings that DNA is very flexible at short length scales. New information about the nanoscale Na+ concentration dependence of DNA flexibility was determined and we show the key role of ApT and TpA steps when it comes to ion-dependent flexibility and melting temperatures.

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Figure 1: Optimized Morse-potential parameters.
Figure 2: Elastic constant, k, as a function of salt concentration.
Figure 3: Equivalent elastic constants, keq, for promoter regions.

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Acknowledgements

We acknowledge financial support by Fapemig and CNPq. G.W. would like to thank R. Guerra-Sá for helpful discussions on TATA-box binding proteins.

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Contributions

G.W. conceived the method and carried out the calculation. C.N. and J.W.E. contributed with the biochemical interpretation of the data and gave conceptual advice. All authors wrote the paper.

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Correspondence to Gerald Weber.

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Weber, G., Essex, J. & Neylon, C. Probing the microscopic flexibility of DNA from melting temperatures. Nature Phys 5, 769–773 (2009). https://doi.org/10.1038/nphys1371

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