Influence of mobile DNA-protein-DNA bridges on DNA configurations: Coarse-grained Monte-Carlo simulations

Abstract

A large literature exists on modeling the influence of sequence-specific DNA-binding proteins on the shape of the DNA double helix in terms of one or a few fixed constraints. This approach is inadequate for the many proteins that bind DNA sequence independently, and that are present in very large quantities rather than as a few copies, such as the nucleoid proteins in bacterial cells. The influence of such proteins on DNA configurations is better modeled in terms of a great number of mobile constraints on the DNA. Types of constraints that mimic the influence of various known non-specifically DNA binding proteins include DNA bending, wrapping, and bridging. Using Monte-Carlo simulations, we here investigate the influence of (non-interacting) mobile DNA-protein-DNA bridges on the configurations of a 1000 bp piece of linear DNA, for both homogeneous DNA and DNA with an intrinsic planar bend. Results are compared to experimental data on the bacterial nucleoid protein H-NS that forms DNA-protein-DNA bridges. In agreement with data on H-NS, we find very strong positioning of DNA-protein-DNA bridges in the vicinity of planar bends. H-NS binds to DNA very cooperatively, but for non-interacting bridges we only find a moderate DNA-induced clustering. Finally, it has been suggested that H-NS is an important contributor to the extreme condensation of bacterial DNA into a nucleoid structure, but we find only a moderate compaction of DNA coils with increasing numbers of non-interacting bridges. Our results illustrate the importance of quantifying the various effects on DNA configurations that have been proposed for proteins that bind DNA sequence independently.