pdf, 9 MiB - Infoscience - EPFL

Parallel scientific activity
In parallel to my thesis scientific work, I have also research interests in complex biological
systems, like DNA. The tools used in this activity are essentially numerical (Polymer Monte-
Carlo simulations, 3D surface construction, bezier curve interpolation), and mathematics (Knot
Topology, Fluid Dynamics) but also consist of some engineering (stereo-lithography
technique). This scientific activity has focused on the following fields (reference numbers
relate to the List of publications hereafter):
3. Physics of DNA knots
o DNA knot dynamics and collisions. Gel electrophoresis allows one to separate
knotted DNA (nicked circular) of equal length according to the knot type. At
low electric fields, complex knots, being more compact, drift faster than simpler
knots. Recent experiments have shown that the drift velocity dependence on the
knot type is inverted when changing from low to high electric fields. We have
presented a computer simulation on a lattice of a closed, knotted, charged DNA
chain drifting in an external electric field in a topologically restricted medium.
Using a Monte Carlo algorithm, the dependence of the electrophoretic migration
of the DNA molecules on the knot type and on the electric field intensity is
investigated. Moreover, we have observed that at high electric fields the
simulated knotted molecules tend to hang over the gel fibres and require passing
over a substantial energy barrier to slip over the impeding gel fibre. At low
electric field the interactions of drifting molecules with the gel fibres are weak
and there are no significant energy barriers that oppose the detachment of
knotted molecules from transverse gel fibres [3,4,7]. At present time,
macroscopic experiments of plastic models of DNA knots falling under gravity
in a very viscuous medium are performed. Such experiments, performed at very
low Reynolds number, could simulate the behaviour of DNA knots inside the
biological cell moving under an electric field during gel electrophoresis.
o DNA disentanglement. Type-2 DNA topoisomerases maintain the level of
DNA knotting up to 80-times lower than the topological equilibrium that would
result from random inter-segmental passages occurring within freely fluctuating
DNA molecules. Keeping the level of DNA knotting below the topological
equilibrium is not a paradox as these enzymes use the energy of ATP hydrolyzis
for each inter-segmental passage. However, it is unknown how these enzymes
that interact with a small portion of knotted circular DNA molecule can
recognize whether a given intersegmental passage will rather lead to a
simplification than to a complication of DNA topology. Over the years several
different mechanisms were proposed to explain the selective simplification of
DNA topology by DNA topoisomerases. We study at present time realistic
simulations of DNA unknotting and find results in agreements with experiments
for realistic geometries.