Facilitated diffusion on mobile DNA: configurational traps and sequence heterogeneity

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.

References in corpus (13)

• First-passage times in complex scale-invariant media
• Kinetics of protein-DNA interaction: facilitated target location in sequence-dependent potential
• Physical Constraints and Functional Characteristics of Transcription Factor-DNA Interaction
• Classes of fast and specific search mechanisms for proteins on DNA
• Searching fast for a target on a DNA without falling to traps
• Facilitated diffusion of proteins on chromatin
• Facilitated diffusion of DNA-binding proteins
• Effects of intersegmental transfers on target location by proteins
• Description of non-specific DNA-protein interaction and facilitated diffusion with a dynamical model
• Facilitated diffusion on confined DNA
• Target search on a dynamic DNA molecule
• Facilitated diffusion of DNA-binding proteins: Simulation of large systems
• Facilitated diffusion of DNA-binding proteins: Efficient simulation with the method of excess collisions (MEC)

Cited by in corpus (13)

• Distance matters: the impact of gene proximity in bacterial gene regulation
• Intracellular facilitated diffusion: searchers, crowders and blockers
• The effects of transcription factor competition on gene regulation
• Energetic funnel facilitates facilitated diffusion
• Optimization and universality of Brownian search in quenched heterogeneous media
• Sequence Heterogeneity Accelerates Protein Search for Targets on DNA
• Physical constraints determine the logic of bacterial promoter architectures
• Protein search for multiple targets on DNA
• Coarse-grained modeling of protein unspecifically bound to DNA
• Dynamical density functional theory for the diffusion of injected Brownian particles
• Can molecular dynamics be used to simulate biomolecular recognition?
• A nonequilibrium strategy for fast target search on the genome
• Modelling chromosome-wide target search