Effects of Protein-Induced Local Bending and Sequence Dependence on the Configurations of Supercoiled DNA Minicircles.

The statistical mechanics of a short circularized DNA molecule, a DNA minicircle, with a prescribed linking number depends heavily on the mechanical and geometrical properties of the DNA, which are known to be functions of the sequence. A description of a general numerical scheme used for the performed advanced simulation is presented with examples that reveal the effects of sequence dependence and local deformations, caused by protein binding, on the configurations in a canonical ensemble of a supercoiled minicircle. Using a realistic course grain model in which the sequence-dependent elasticity, the intramolecular electrostatic interactions, and the impenetrability of the DNA molecule are taken into account, the bifurcation of equilibria of supercoiled minicircle DNA with the induced bending as a parameter is shown. The unique Monte Carlo scheme for constrained DNA molecules was utilized in order to calculate site-to-site distance probabilities for each pair of sites in the molecule. The simulated examples show not only that the sequence alone can play a significant role in bringing two remote sites to a contact but also the possible existence of several competing regions of contact. The results suggest that the local deformation caused by protein binding can yield a global configurational change, dominated by slithering motion, which brings two (originally) remote sites to close proximity, and that the nature of such effect is related to the sequence architecture.