Paper Citing NAMD - Abstract
Lockhart, Christopher; Klimov, Dmitri K.
Binding of A beta peptide creates lipid density depression in DMPC bilayer
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1838:2678-2688, OCT 2014
Using isobaric-isothermal replica exchange molecular dynamics and all-atom explicit water model we study the impact of A beta monomer binding on the equilibrium properties of DMPC bilayer. We found that partial insertion of A beta peptide into the bilayer reduces the density of lipids in the binding "footprint" and indents the bilayer thus creating a lipid density depression. Our simulations also reveal thinning of the bilayer and a decrease in the area per lipid in the proximity of A beta. Although structural analysis of lipid hydrophobic core detects disordering in the orientations of lipid tails, it also shows surprisingly minor structural perturbations in the tail conformations. Finally, partial insertion of A beta monomer does not enhance water permeation through the DMPC bilayer and even causes considerable dehydration of the lipid-water interface. Therefore, we conclude that A beta monomer bound to the DMPC bilayer fails to perturb the bilayer structure in both leaflets. Limited scope of structural perturbations in the DMPC bilayer caused by A beta monomer may constitute the molecular basis of its low cytotoxicity. (C) 2014 Elsevier B.V. All rights reserved.
