DNA Internal Motion Likely Accelerates Protein Target Search in a Packed Nucleoid

Transcription factors must diffuse through densely packed and coiled DNA to find their binding sites. Using a coarse-grained model of DNA and lac repressor (Lacl) in the Escherichia coli nucleoid, simulations were performed to examine how Lac! diffuses in such a space. Despite the canonical picture of Lac! diffusing rather freely, in reality the DNA is densely packed, is not rigid but highly mobile, and the dynamics of DNA dictates to a great extent the Lacl motion. A possibly better picture of unbound Lac! motion is that of gated diffusion, where DNA confines Lac! in a cage, but Lacl can move between cages when hindering DNA strands move out of the way. Three-dimensional diffusion constants for unbound Lacl computed from simulations closely match those for unbound Lacl in vivo reported in the literature. The internal motions of DNA appear to be governed by strong internal forces arising from being crowded into the small space of the nucleoid. A consequence of the DNA internal motion is that protein target search may be accelerated.