Description of nonspecific DNA-protein interaction and facilitated diffusion with a dynamical model

Abstract

We propose a dynamical model for nonspecific DNA-protein interaction, which is based on the "bead-spring" model previously developed by other groups, and investigate its properties using Brownian dynamics simulations. We show that the model successfully reproduces some of the observed properties of real systems and predictions of kinetic models. For example, sampling of the DNA sequence by the protein proceeds via a succession of three-dimensional motion in the solvent, one-dimensional sliding along the sequence, short hops between neighboring sites, and intersegmental transfers. Moreover, facilitated diffusion takes place in a certain range of values of the protein effective charge, that is, the combination of one-dimensional sliding and three-dimensional motion leads to faster DNA sampling than pure three-dimensional motion. At last, the number of base pairs visited during a sliding event is comparable to the values deduced from single-molecule experiments. We also point out and discuss some discrepancies between the predictions of this model and some recent experimental results as well as some hypotheses and predictions of kinetic models.

Dynamical model of DNA-protein interaction: Effect of protein charge distribution and mechanical properties

“…(2.5), while they were considered as positive quantities in eq. (2.6) of [20]. This is the reason why there was a minus sign in the expression for ) ( ev p E in our first study, while there is none in the present work.…”

“…As discussed in [20], DNA is not modeled as a single long chain, in order to avoid excessive DNA curvature at the cell walls. It is instead modeled as a set of While proteins were taken as single beads in [20], they are modeled in the present work by sets of 13 beads with hydrodynamic radius 5 . 3 prot = a nm interconnected by elastic bonds.…”

“…(2.7) of [20], is the repulsive part of a Lennard-Jones-like potential function. Note that charges are taken as signed quantities in eq.…”

“…The confinement potential wall V is taken, as in [20], as a sum of repulsive terms that act on the beads that trespass the radius 0 R and repel them inside the sphere:…”

Protein–DNA Electrostatics

“…This also gives a rational basis to some ad-hoc protein sizes that had to be put by hand in recent coarse grained simulations of protein sliding on DNA to ensure the protein would not go closer to DNA than the distance observed in the non-specific complex [81,82,83].…”