Publication details

Mechanical Model of DNA Allostery

Authors

DRŠATA Tomáš ZGARBOVÁ Marie ŠPAČKOVÁ Naděžda JUREČKA Petr ŠPONER Jiří LANKAŠ Filip

Type Article in Periodical
Magazine / Source Journal of Physical Chemistry Letters
MU Faculty or unit

Central European Institute of Technology

Citation
Web http://pubs.acs.org/doi/abs/10.1021/jz501826q
Doi http://dx.doi.org/10.1021/jz501826q
Field Physical chemistry and theoretical chemistry
Keywords MOLECULAR-DYNAMICS SIMULATIONS; MINOR-GROOVE BINDERS; PYRROLE-IMIDAZOLE POLYAMIDE; BASE-PAIR LEVEL; B-DNA; A-TRACTS; BINDING; DEFORMABILITY; PROTEIN; COMPLEXES
Description 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. [GRAPHICS]
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