title: DNA-binding protein searches for its target: Non-monotonic dependence of the search time on the density of roadblocks bound on the DNA chain.
abstract: The search of DNA-binding proteins for their target sites positioned on DNA plays a very important role in many cellular processes, and this search process combines 3D excursions in the bulk solution with one-dimensional sliding along the DNA chain. In living cells, there exist roadblocks along DNA chain formed by other proteins; however, the role of the roadblock in search rate is poorly understood. Based on 3D Langevin dynamics simulations, we have investigated the effect of the blocker on the search dynamics. For a pair of symmetrically placed blockers with respect to the target, we find that, with increasing the distance between the blocker and the target, the search time, τ, rapidly decreases and then saturates. For randomly placed blockers with density ϕ, τ may initially increase to its maximum and then unexpectedly decreases with increasing ϕ, or always increase with ϕ, depending on the nonspecific interaction strength and the volume fraction of DNA in the system. The previous contradicted results on the role of the blocker in search time are reconciled by these findings. Particularly, the nonmonotonic behavior of τ with ϕ indicates that blockers may facilitate the search after a critical ϕ.
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Collaborative Innovation Center of Chemistry for Energy Materials, and Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui Province 230026, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Collaborative Innovation Center of Chemistry for Energy Materials, and Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui Province 230026, People's Republic of China.
authors.forename: Kaifu
authors.initials: K
authors.lastname: Luo
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D004058:Diffusion; D008956:Models, Chemical; D008957:Models, Genetic; D011485:Protein Binding; D013997:Time Factors
chemical_list: D004268:DNA-Binding Proteins; D004247:DNA