Non-specific DNA-protein interaction: Why proteins can diffuse along DNA

Abstract

The structure of DNA Binding Proteins enables a strong interaction with their specific target site on DNA. However, recent single molecule experiment reported that proteins can diffuse on DNA. This suggests that the interactions between proteins and DNA play a role during the target search even far from the specific site. It is unclear how these non-specific interactions optimize the search process, and how the protein structure comes into play. Each nucleotide being negatively charged, one may think that the positive surface of DNA-BPs should electrostatically collapse onto DNA. Here we show by means of Monte Carlo simulations and analytical calculations that a counter-intuitive repulsion between the two oppositely charged macromolecules exists at a nanometer range. We also show that this repulsion is due to a local increase of the osmotic pressure exerted by the ions which are trapped at the interface. For the concave shape of DNA-BPs, and for realistic protein charge densities, we find that the repulsion pushes the protein in a free energy minimum at a distance from DNA. As a consequence, a favourable path exists along which proteins can slide without interacting with the DNA bases. When a protein encounters its target, the osmotic barrier is completely counter-balanced by the H-bond interaction, thus enabling the sequence recognition.

4 pages, 4 figures, submitted to PRL

References in corpus (2)

• Kinetics of protein-DNA interaction: facilitated target location in sequence-dependent potential
• Electrostatic Interactions of Asymmetrically Charged Membranes

Cited by in corpus (10)

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• Dynamical model of DNA-protein interaction: effect of protein charge distribution and mechanical properties
• Mesoscopic Model for Free Energy Landscape Analysis of DNA sequences
• A mini-review of the diffusion dynamics of DNA-binding proteins: Experiments and models
• Poisson-Boltzmann for oppositely charged bodies: an explicit derivation
• Distribution of counterions and interaction between two similarly charged dielectric slabs: Roles of charge discreteness and dielectric inhomogeneity
• Interaction regimes for oppositely charged plates with multivalent counterions