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Disparity in anomalous diffusion of proteins searching for their target DNA sites in a crowded medium is controlled by the size, shape and mobility of macromolecular crowders

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Abstract

Using extensive computer simulations, we analyzed the role of physical properties of molecular crowding agents such as size, shape and mobility in the target search dynamics of DNA binding proteins. Our main result is that the sub-diffusive dynamics of a protein inside a crowded medium strongly depends on the crowder properties and also on the protein's mode of diffusion. For instance, while scanning the DNA one-dimensionally, the protein dynamics does not vary with the change in crowder properties. Conversely, the diffusion exponent varies non-monotonically during 3D diffusion and is maximally affected when the crowders match the protein physically. The investigation shows that the effect stems from the ruggedness of the associated potential energy landscape, which is regulated by the protein–crowder and DNA–crowder interactions. Our findings have broad significance in understanding the target search dynamics of proteins on DNA in crowded cellular milieu and selecting appropriate crowding agents when designing in vitro experiments.

Graphical abstract: Disparity in anomalous diffusion of proteins searching for their target DNA sites in a crowded medium is controlled by the size, shape and mobility of macromolecular crowders

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Publication details

The article was received on 21 Sep 2018, accepted on 02 Dec 2018 and first published on 03 Dec 2018


Article type: Paper
DOI: 10.1039/C8SM01933A
Citation: Soft Matter, 2019, Advance Article
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    Disparity in anomalous diffusion of proteins searching for their target DNA sites in a crowded medium is controlled by the size, shape and mobility of macromolecular crowders

    P. Dey and A. Bhattacherjee, Soft Matter, 2019, Advance Article , DOI: 10.1039/C8SM01933A

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