title: Mechanism of Facilitated Diffusion during a DNA Search in Crowded Environments.
abstract: The key feature explaining the rapid recognition of a DNA target site by its protein lies in the combination of one- and three-dimensional (1D and 3D) diffusion, which allows efficient scanning of the many alternative sites. This facilitated diffusion mechanism is expected to be affected by cellular conditions, particularly crowding, given that up to 40% of the total cellular volume may by occupied by macromolecules. Using coarse-grained molecular dynamics and Monte Carlo simulations, we show that the crowding particles can enhance facilitated diffusion and accelerate search kinetics. This effect originates from a trade-off between 3D and 1D diffusion. The 3D diffusion coefficient is lower under crowded conditions, but it has little influence because the excluded volume effect of molecular crowding restricts its use. Largely prevented from using 3D diffusion, the searching protein dramatically increases its use of the hopping search mode, which results in a higher linear diffusion coefficient. The coefficient of linear diffusion also increases under crowded conditions as a result of increased collisions between the crowding particles and the searching protein. Overall, less 3D diffusion coupled with an increase in the use of the hopping and speed of 1D diffusion results in faster search kinetics under crowded conditions. Our study shows that the search kinetics and mechanism are modulated not only by the crowding occupancy but also by the properties of the crowding particles and the salt concentration.
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science , Rehovot 76100, Israel.
authors.forename: Dana
authors.initials: D
authors.lastname: Krepel
authors.affiliation: Max Planck Institute of Colloids and Interfaces , Science Park Golm, 14424 Potsdam, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Gomez
authors.affiliation: Max Planck Institute of Colloids and Interfaces , Science Park Golm, 14424 Potsdam, Germany.|Institute for Nonlinear Dynamics, Georg-August University Göttingen , Friedrich-Hund-Platz 1, 37077 Göttingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Klumpp
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science , Rehovot 76100, Israel.
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Levy
mesh_terms: D004247:DNA / Q000737:chemistry*; D004058:Diffusion; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method
chemical_list: D004247:DNA