A Glycam-Based Force Field
for Simulations of Lipopolysaccharide
Membranes: Parametrization and Validation
Posted on 2012-11-13 - 00:00
Lipopolysaccharides (LPS) comprise the outermost layer
of the Gram-negative
bacteria cell envelope. Packed onto a lipid layer, the outer membrane
displays remarkable physical–chemical differences compared
to cell membranes. The carbohydrate-rich region confers a membrane
asymmetry that underlies many biological processes such as endotoxicity,
antibiotic resistance, and cell adhesion. Furthermore, unlike membrane
proteins from other sources, integral outer-membrane proteins do not
consist of transmembrane α helices; instead they consist of
antiparallel β-barrels, which highlights the importance of the
LPS membrane as a medium. In this work, we present an extension of
the GLYCAM06 force field that has been specifically developed for
LPS membranes using our Wolf2Pack program. This new set
of parameters for lipopolysaccharide molecules expands the GLYCAM06
repertoire of monosaccharides to include phosphorylated N- and O-acetylglucosamine, 3-deoxy-d-manno-oct-2-ulosonic acid, l-glycero-D-manno-heptose and its O-carbamoylated variant, and N-alanine-d-galactosamine. A total of 1 μs
of molecular dynamics simulations of the rough LPS membrane of Pseudomonas aeruginosa PA01 is used to showcase the
added parameter set. The equilibration of the LPS membrane is shown
to be significantly slower compared to phospholipid membranes, on
the order of 500 ns. It is further shown that water molecules penetrate
the hydrocarbon region up to the terminal methyl groups, much deeper
than commonly observed for phospholipid bilayers, and in agreement
with neutron diffraction measurements. A comparison of simulated structural,
dynamical, and electrostatic properties against corresponding experimentally
available data shows that the present parameter set reproduces well
the overall structure and the permeability of LPS membranes in the
liquid-crystalline phase.
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Kirschner, Karl N.; Lins, Roberto D.; Maass, Astrid; Soares, Thereza A. (2016). A Glycam-Based Force Field
for Simulations of Lipopolysaccharide
Membranes: Parametrization and Validation. ACS Publications. Collection. https://doi.org/10.1021/ct300534j
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AUTHORS (4)
KK
Karl N. Kirschner
RL
Roberto D. Lins
AM
Astrid Maass
TS
Thereza A. Soares