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Acceleration of bursty multiprotein target search kinetics on DNA by colocalisation

Kar, P and Cherstvy, AG and Metzler, R (2017) Acceleration of bursty multiprotein target search kinetics on DNA by colocalisation. In: Physical Chemistry Chemical Physics, 20 (12). pp. 7931-7946.

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Official URL: https://doi.org/10.1039/c7cp06922g


Proteins are capable of locating specific targets on DNA by employing a facilitated diffusion process with intermittent 1D and 3D search steps. Gene colocalisation and coregulation - i.e. the spatial proximity of two communicating genes - is one factor capable of accelerating the target search process along the DNA. We perform Monte Carlo computer simulations and demonstrate the benefits of gene colocalisation for minimising the search time in a model DNA-protein system. We use a simple diffusion model to mimic the search for targets by proteins, produced initially in bursts of multiple proteins and performing the first-passage search on the DNA chain. The behaviour of the mean first-passage times to the target is studied as a function of distance between the initial position of proteins and the DNA target position, as well as versus the concentration of proteins. We also examine the properties of bursty target search kinetics for varying physical-chemical protein-DNA binding affinity. Our findings underline the relevance of colocalisation of production and binding sites for protein search inside biological cells.

Item Type: Journal Article
Publication: Physical Chemistry Chemical Physics
Publisher: Royal Society of Chemistry
Additional Information: The copyright for this article belongs to the Owner Societies.
Keywords: DNA; DNA binding protein; protein binding, binding site; chemistry; computer simulation; diffusion; kinetics; molecular model; Monte Carlo method; thermodynamics, Binding Sites; Computer Simulation; Diffusion; DNA; DNA-Binding Proteins; Kinetics; Models, Molecular; Monte Carlo Method; Protein Binding; Thermodynamics
Department/Centre: Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited: 22 Aug 2022 06:47
Last Modified: 22 Aug 2022 06:47
URI: https://eprints.iisc.ac.in/id/eprint/76107

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