Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey - page 54

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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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