Facilitated diffusion on mobile DNA: configurational traps and sequence heterogeneity

TL;DR

This study uses Brownian dynamics simulations to explore how DNA organization and sequence heterogeneity influence protein search efficiency along DNA, revealing that topology and traps can both hinder and enhance facilitated diffusion.

Contribution

It introduces a detailed simulation model considering DNA topology and sequence heterogeneity, highlighting their complex effects on facilitated diffusion.

Findings

DNA loop networks affect target search sensitivity to spatial location

Sequence heterogeneity can create traps that slow diffusion

Properly positioned traps can improve search efficiency

Abstract

We present Brownian dynamics simulations of the facilitated diffusion of a protein, modelled as a sphere with a binding site on its surface, along DNA, modelled as a semi-flexible polymer. We consider both the effect of DNA organisation in 3D, and of sequence heterogeneity. We find that in a network of DNA loops, as are thought to be present in bacterial DNA, the search process is very sensitive to the spatial location of the target within such loops. Therefore, specific genes might be repressed or promoted by changing the local topology of the genome. On the other hand, sequence heterogeneity creates traps which normally slow down facilitated diffusion. When suitably positioned, though, these traps can, surprisingly, render the search process much more efficient.