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J Phys Chem Lett. 2014 Nov 6;5(21):3831-5. doi: 10.1021/jz501826q. Epub 2014 Oct 21.

Mechanical Model of DNA Allostery.

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†Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague, Czech Republic.
‡Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University Prague, Albertov 6, 128 43 Prague, Czech Republic.
§Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University, 17. listopadu 12, 771 46 Olomouc, Czech Republic.
∥Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 612 65 Brno, Czech Republic.
⊥Department of Condensed Matter Physics, Faculty of Science, Masaryk University, Kotlářská 2, 611 37 Brno, Czech Republic.
#CEITEC - Central European Institute of Technology, Campus Bohunice, Kamenice 5, 625 00 Brno, Czech Republic.


The importance of allosteric effects in DNA is becoming increasingly appreciated, but the underlying mechanisms remain poorly understood. In this work, we propose a general modeling framework to study DNA allostery. We describe DNA in a coarse-grained manner by intra-base pair and base pair step coordinates, complemented by groove widths. Quadratic deformation energy is assumed, yielding linear relations between the constraints and their effect. Model parameters are inferred from standard unrestrained, explicit-solvent molecular dynamics simulations of naked DNA. We applied the approach to study minor groove binding of diamidines and pyrrole-imidazole polyamides. The predicted DNA bending is in quantitative agreement with experiment and suggests that diamidine binding to the alternating TA sequence brings the DNA closer to the A-tract conformation, with potentially important functional consequences. The approach can be readily applied to other allosteric effects in DNA and generalized to model allostery in various molecular systems.


A-tract; Amber; coarse-grained model; fluctuation theory; minor groove binder; molecular dynamics simulations


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