ci0c00267_si_001.pdf (1.02 MB)
Impact of A2V Mutation and Histidine Tautomerism on Aβ42 Monomer Structures from Atomistic Simulations
journal contribution
posted on 2020-06-30, 22:03 authored by Hao Li, Yeonsig Nam, Abbas Salimi, Jin Yong LeeThe self-assembly of amyloid-β
(Aβ) peptides into senile
plaques in the brain is a hallmark of Alzheimer’s disease (AD)
pathology. Mutation and histidine tautomerism are considered intrinsic
origins in the accumulation of Aβ. As a first step toward understanding
the impact of A2V mutation and histidine tautomerism on the Aβ42
isoform, we performed replica-exchange molecular dynamics (REMD) simulations
to investigate the effects of histidine tautomerism on the structural
properties of A2V Aβ42 peptides. There are generally more β-sheet
and less α-helix secondary structures in A2V Aβ42 monomers
than in WT Aβ42, implying a higher aggregation tendency in A2V
Aβ42, which is consistent with previous studies. The current
research will help develop the histidine tautomerism hypothesis of
misfolded protein aggregation and eventually elucidate the pathogenesis
of AD.