Molecular simulations of DNA-binding proteins dissociating from a self-avoiding bacterial chromosome.

By using extensive coarse-grained molecular simulations, we model the unbinding of specific and nonspecific dimeric DNA-binding proteins from a high-molecular-weight circular DNA molecule in a cylindrical structure mimicking the cellular confinement of a bacterial chromosome. Our simulations show that a concentration-dependent dissociation phenomenon, referred to as facilitated dissociation, can occur at physiological protein concentrations. When tens of micromolar protein concentrations (e.g., peaks levels of Fis protein in nutrient-rich conditions) are emulated, proteins significantly change the chromosome structure by forming dense protein clusters bridging specific sites or juxtaposing remote DNA segments. These structures, depending on the proteins’ binding specificity, either increase or decrease the protein off-rates (i.e., the inverse residence time of the protein on DNA). Overall, our results indicate that the cellular-concentration level of a structural DNA-binding protein is intermingled with the genome architecture and DNA-residence times, thereby providing a basis for understanding the complex effects of dynamic protein-DNA interactions on gene regulation.