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Compaction and flexibility of the DNA
Recently, an intriguing
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
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,
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.