Speaker
Description
The formation of beta-sheet-rich toxic oligomers of the amyloid-beta (Abeta) peptide is mediated by the
interaction of the peptide with the GM1 gangliosides[1]. These sugar-containing glycolipids
structures introduce a third macromolecule, carbohydrates, to further complicate the interactions
between peptide and lipid bilayer. Although atomistic molecular dynamics (MD) simulations is
an ideal tool for characterizing this system, the ability of the two most popular force fields,
CHARMM and Amber, to model these systems has yet to be compared. Systems comprised of
Abeta and bilayers comprised of GM1 in DOPC were constructed and represented with four force
fields – CHARMM36, CHARMM36m, Amber99SB*-ILDN with Robert Best correction, and
Amber14SB. Three (3) x 500 ns simulations were carried out on each system, and the sampling
of each were compared to Hamiltonian replica-exchange simulations of equal trajectory length.
A detailed analysis of the interactions between peptide, membrane and ganglioside will be
presented.
