title: Method for the analysis of contribution of sliding and hopping to a facilitated diffusion of DNA-binding protein: Application to in vivo data.
abstract: DNA-binding protein searches for its target, a specific site on DNA, by means of diffusion. The search process consists of many recurrent steps of one-dimensional diffusion (sliding) along the DNA chain and three-dimensional diffusion (hopping) after dissociation of a protein from the DNA chain. Here we propose a computational method that allows extracting the contribution of sliding and hopping to the search process in vivo from the measurements of the kinetics of the target search by the lac repressor in Escherichia coli [P. Hammar et al., Science 336, 1595 (2012)]. The method combines lattice Monte Carlo simulations with the Brownian excursion theory and includes explicitly steric constraints for hopping due to the helical structure of DNA. The simulation results including all experimental data reveal that the in vivo target search is dominated by sliding. The short-range hopping to the same base pair interrupts one-dimensional sliding while long-range hopping does not contribute significantly to the kinetics of the search of the target in vivo.
authors.affiliation: Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Tabaka
authors.affiliation: Department of Mathematics, University of Washington, Box 354350, Seattle, Washington 98195, USA.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Burdzy
authors.affiliation: Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Hołyst
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000737:chemistry*; D055459:Facilitated Diffusion; D007700:Kinetics; D056968:Lac Repressors / Q000737:chemistry*; D008956:Models, Chemical; D008957:Models, Genetic; D009010:Monte Carlo Method; D009690:Nucleic Acid Conformation; D011485:Protein Binding
chemical_list: D029968:Escherichia coli Proteins; D056968:Lac Repressors; C539064:LacI protein, E coli; D004247:DNA