C. Micheletti, D. Marenduzzo, E. Orlandini and D.W. Sumners
Simulations of knotting in confined circular DNA
Biophys. J. 95 3591 (2008)
Link to online article.
The packing of DNA inside bacteriophages arguably yields
the simplest example of genome organisation in living organisms. As an
assay of packing geometry, the DNA knot spectrum produced upon release
of viral DNA from the P4 phage capsid has been analyzed, and compared
to results of simulation of knots in confined volumes. We present new
results from extensive stochastic sampling of confined self-avoiding
and semi-flexible circular chains with volume exclusion. The physical
parameters of the chains (contour length, cross section and bending
rigidity) have been set to match those of P4 bacteriophage DNA. By
using advanced sampling techniques, involving multiple Markov chain
pressure-driven confinement combined with a thermodynamic reweighting
technique, we establish the knot spectrum of the circular chains for increasing
confinement up to the highest densities for which available algorithms
can exactly classify the knots. Compactified configurations have
enclosing hull diameter about 2.5 times larger that the P4 calliper
size. The results are discussed in relation to the recent experiments
on DNA knotting inside the capsid of a P4 tailless mutant. Our
investigation indicates that confinement favours chiral knots over
achiral ones, as found in the experiments. However, no significant
bias of torus over twist knots is found, contrary to the P4
results. The result poses a crucial question for future studies of DNA
packaging in P4: is the discrepancy due to the insufficient
confinement of the equilibrium simulation or does it indicate that
out-of-equilibrium mechanisms (such as rotation by packaging motors)
affect the genome organization, hence its knot spectrum in P4?