Modelling DNA loops using continuum and statistical mechanics.

The classical Kirchhoff elastic-rod model applied to DNA is extended to account for sequence-dependent intrinsic twist and curvature, anisotropic bending rigidity, electrostatic force interactions, and overdamped Brownian motion in a solvent. The zero-temperature equilibrium rod model is then applied to study the structural basis of the function of the lac repressor protein in the lac operon of Escherichia coli. The structure of a DNA loop induced by the clamping of two distant DNA operator sites by lac repressor is investigated and the optimal geometries for the loop of length 76 bp are predicted. Further, the mimicked binding of catabolite gene activator protein (CAP) inside the loop provides solutions that might explain the experimentally observed synergy in DNA binding between the two proteins. Finally, a combined Monte Carlo and Brownian dynamics solver for a worm-like chain model is described and a preliminary analysis of DNA loop-formation kinetics is presented.