Influence of electric field on the amyloid-β(29-42) peptides embedded in a membrane bilayer.
Yan LuXiao-Feng ShiFreddie R SalsburyPhilippe DerreumauxPublished in: The Journal of chemical physics (2018)
Alzheimer's disease is linked to various types of aggregates of amyloid-β (Aβ) peptide and their interactions with protein receptors and neuronal cell membranes. Little is known on the impact of the electric field on membrane-embedded Aβ. Here we use atomistic molecular dynamics simulations to study the effects of a constant electric field on the conformations of Aβ29-42 dimer inside a membrane, where the electric field has a strength of 20 mV/nm which exists across the membrane of a human neuron. Starting from α-helix peptides, the transmembrane electric field (TMEF) accelerates the conversion from the Gly-out substate to the Gly-side and Gly-in substates. Starting from β-sheet peptides, TMEF induces changes of the kink and tilt angles at Gly33 and Gly37. Overall, in the simulations totaling 10 μs, TMEF establishes new ground states for the dimer, similar to induced-fit in ligand binding. Our findings indicate that TMEF can stabilize rare conformations of amyloid peptides, and this could influence the cleavage of the amyloid precursor protein and the formation of β-sheet oligomers in membrane bilayers.
Keyphrases
- molecular dynamics simulations
- amino acid
- endothelial cells
- molecular docking
- molecular dynamics
- photodynamic therapy
- cell therapy
- oxidative stress
- mesenchymal stem cells
- diabetic rats
- binding protein
- brain injury
- small molecule
- subarachnoid hemorrhage
- blood brain barrier
- mild cognitive impairment
- pluripotent stem cells
- cerebral ischemia