A computational study of nucleosomal DNA flexibility
Jory Z Ruscio 1 and Alexey V Onufriev 1*
1 Virginia Tech
* To whom correspondence should be addressed. E-mail: alexey{at}cs.vt.edu.
Submitted on February 2, 2006
Revised on February 28, 2006
Accepted on 5 July 2006
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Abstract |
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Molecular dynamics simulations of the nucleosome core particle and its isolated DNA free in solution are reported. The simulations are based on the implicit solvent methodology and provide insights into the nature of large-scale structural fluctuations and flexibility of the nucleosomal DNA. In addition to the kinked regions previously identified in the Richmond et al. X-ray structure of the nucleosome, the simulations support the existence of a biochemically identified distorted region of the DNA. Comparison of computed relative free energies shows that formation of the kinks is associated with little, if any, energy cost relative to a smooth, ideal conformation of the DNA superhelix. Isolated nucleosomal DNA is found to be considerably more flexible than expected for a 147 bp stretch of DNA based on its canonical persistence length of 500 Å. Notably, the considerable bending of the DNA observed in our simulations occurs without breaking of Watson-Crick bonds. The computed relative stability of bent conformations is sensitive to the ionic strength of the solution in the physiological range; the sensitivity suggests possible experiments that might provide further insights into the structural origins of the unusual flexibility of the DNA.
Key Words:
DNA, energetics, flexibility, implicit solvent, molecular dynamics, nucleosome
