Paper Citing NAMD - Abstract
Lockhart, Christopher; Klimov, Dmitri K.
Alzheimer's A beta 10-40 Peptide Binds and Penetrates DMPC Bilayer: An Isobaric-Isothermal Replica Exchange Molecular Dynamics Study
JOURNAL OF PHYSICAL CHEMISTRY B, 118:2638-2648, MAR 13 2014
Using all-atom explicit solvent model and isobaric isothermal replica exchange molecular dynamics, we studied binding of A beta 10-40 monomers to zwitterionic DMPC bilayer. Our simulations suggest three main conclusions. First, binding of A beta 10-40 monomer to the DMPC bilayer causes dramatic structural transition in the peptide resulting in the formation of stable helical structure in the C-terminal. In addition, binding to the lipid bilayer induces the formation of intrapeptide Asp23-Lys28 salt bridge. We argue that the emergence of helix is the consequence of hidden helix propensity harbored in the A beta 10-40 C-terminal. This propensity is revealed by the lipids cross-bridging amino acids in helical conformations and by significant hydrophobic moment of the C-terminal. Second, the central hydrophobic cluster and, particularly, the C-terminal of A beta 10-40 not only govern binding to the bilayer but also penetrate into bilayer core. In contrast, the polar N-terminal and turn region form interactions mainly with the bilayer surface. Third, our simulations suggest that upon A beta 10-40 binding to the bilayer a highly heterogeneous local environment emerges along A beta 10-40 chain. The N-terminal is ex-posed to polar well-hydrated medium, whereas the C-terminal is largely shielded from water residing in mostly hydrophobic environment. The implication of our results is that A beta aggregation mediated by zwitterionic lipid bilayer is likely to be different from that in bulk water.
