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Abstract:
Abstract:
The subject of this thesis are the interactions between
nucleosome core particles (NCPs). NCPs are the primary storage units
of DNA in eucaryotic cells. Each NCP consists of a core of eight
histone proteins and a strand of DNA, which is wrapped around about
two times.
Each histone protein has a terminal tail passing over and
between the superhelix of the wrapped DNA.
Special emphasis was
placed on the role of the histone tails, since experimental findings
suggest that the tails have a great influence on the mutual
attraction of the NCPs.
In those experiments Mangenot et al. observe a dramatic change in the
configuration of the tails, which is accompanied by evidence of mutual
attraction between NCPs, when a certain salt concentration is reached.
Existing models used in the theoretical
approaches and in simulations
focus on the description of the histone core and the wrapped
DNA, but neglect the histone tails. We introduce the multi chain
complex as a new simulation model. Here the histone core and the
wrapping DNA are modelled via a charged sphere, while the histone tails
are represented by oppositely charged chains grafted on the sphere
surface.
We start by investigating the parameter space describing a single
NCP. The Debye-H\"uckel potential is used to model the electrostatic
interactions and to determine the effective charge of the NCP core.
This value is subsequently used for a study of the
pair-interaction of two NCPs via an extensive Molecular Dynamics
study.
The monomer distribution of the full chain model is investigated.
The existence of
tail bridges between the cores is demonstrated.
Finally, by discriminating between bridging and non-bridging
configurations, we can show that the
effect of tail bridging between the spheres does indeed account for
the observed attraction.
The full chain model can serve as a model to study the acetylation of
the histone tails of the nucleosome. The reduction of the charge
fraction of the tails, that corresponds to the process of
acetylation, leads to a reduction or even the disappearance of the
attraction. A recent MC study
links
this effect to the unfolding of the chromatin fiber in the
case of acetylated histone tails.
In this case the acetylation of the histone tails leads to the formation
of heterochromatin, and one could understand how larger regions of the
genetic information could be inactivated through this mechanism.
