Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Session IX Abstracts

Modeling the binding of H-NS to AT-rich DNA Eva C. Van Mastbergen, Jocelyne Vreede . University of Amsterdam, Amsterdam, The Netherlands.

Bacteria organize their chromosomal DNA within a structure called the nucleoid, by employing nucleoid-associated proteins. The histone-like nucleoid structuring protein (H-NS) can form bridges between two DNA duplexes, therefore locally reducing the effective volume. H-NS contains an oligomerization region and a DNA-binding domain. H-NS prefers to bind to the minor groove of AT-rich DNA with a loop containing a motif that consists of Glutamine112, Glycine113 and Arginine114. Molecular simulation can complement experiments by modeling the dynamical time evolution of biomolecular systems in atomistic detail. To study the binding mechanism of H-NS to DNA, we performed advanced molecular simulations on a system containing the H-NS DNA binding domain and an AT-rich dsDNA sequence. First, we performed straightforward Molecular Dynamics simulations, followed by biased sampling of association/dissociation using metadynamics. Finally, we obtained unbiased transition paths using transition path sampling. Our results indicate that H-NS binds to the minor groove with residues Q112, G113 and R114, in agreement with experiment. Furthermore, we identified two mechanisms; Q112 binds first, followed by G113 and R114; or R114 binds first, followed by G113 and Q112. The hydrogen bond between G113 and a thymine base is essential in the association and dissociation of H-NS and DNA.

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