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Compaction and flexibility of the DNA


Recently, an intriguing new phenomenon was reported experimentally [see works of J. Widom's group]: on short length scales (~ 100 b.p.) DNA double helix does not behave as a relatively stiff rod, as might be expected based on its conventional persistence length value of ~ 150 b.p. In contrast, short DNA fragments were found to cyclize spontaneously, with an appreciable probability. Exactly how this unusual flexibility is accommodated structurally is not known. Since relatively short, bent DNA fragments participate in many vital biological processes, the issue is important. We use large-scale molecular dynamics simulations to understand the mechanism behind the phenomenon.

The bending of the nucleosomal DNA observed in our simulations.


  • Structural fluctuations of the Nucleosomal DNA. A Movie.
  • This movie shows a 5 ns MD simulation of the nucleosomal DNA (146 bp) at 300K in implicit solvent. To facilitate visual analysis of the structural features, the actual trajectory is played repeatedly many times. Due to the absence of viscosity, the 5ns of the actual simulation time corresponds to a much larger real time, probably in the hundreds of ns. For details, see J. Zmuda and A. Onufriev, ``A computational study of nucleosomal DNA flexibility", Biophys. J. 2006. The authors thank TIZBI, Inc. for the help with the animation and artistic rendering issues.


    Understanding the function of the nucleosome


    Structure of the nucleosome (left) and the predicted diagram of its stability (right).

    Evidence is now overwhelming that not only the sequence, but also the details of DNA packaging inside the cell are an important part of the genetic message. The primary level of DNA compaction in eukareotic organisms in vivo is the nucleosome . At this level, a stretch of 147 base-pairs of the DNA is tightly wrapped 1.65 times around a set of eight proteins that carry the charge opposite of that of the DNA. Details of the nucleosome dynamics are vital for understanding key cellular processes such as DNA replication, repair and transcription. Cell differentiation is also intimately linked with DNA compaction. Despite its importance, the nucleosome system is far from being fully understood. One of the key unanswered questions is the following: how can the whole nucleosome be highly stable, protective of its genetic material, while at the same time its tightly wrapped DNA be highly accessible, easily revealing its information content? We have developed a theoretical model ( Andrew T. Fenley, David A. Adams, and Alexey V. Onufriev. ``Charge State of the Globular Histone Core Controls Stability of the Nucleosome" Biophysical Journal, 99, 1577-1585 (2010)) that addresses these issues.