MODELING CHAIN FOLDING IN PROTEIN-CONSTRAINED CIRCULAR DNA

An efficient method for sampling equilibrium configurations of DNA cha ins binding one or more DNA-bending proteins is presented. The techniq ue is applied to obtain the tertiary structures of minimal bending ene rgy for a selection of dinucleosomal minichromosomes that differ in de gree of protein-DNA interaction, protein spacing along the DNA chain c ontour, and ring size. The protein-bound portions of the DNA chains ar e represented by tight, left-handed supercoils of fixed geometry. The protein-free regions are modeled individually as elastic rods. For eac h random spatial arrangement of the two nucleosomes assumed during a s tochastic search for the global minimum, the paths of the flexible con necting DNA segments are determined through a numerical solution of th e equations of equilibrium for torsionally relaxed elastic rods. The m inimal energy forms reveal how protein binding and spacing and plasmid size differentially affect folding and offer new insights into experi mental minichromosome systems.