Investigations on the Structural Characteristics that Seed the Aggregation of Amyloid-β1-42 Peptide: Insights from Molecular Dynamics Simulations

Author(s): Mary Dutta, Ankita Deb, Mattaparthi Venkata Satish Kumar

Journal Name: Current Proteomics

Volume 13 , Issue 3 , 2016

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Graphical Abstract:


Amyloid β-peptide (Aβ1-42) is known to be the primary component of the amyloid plaques found in the brain of patients suffering from Alzheimer’s disease (AD). Extensive research has been done in the past with respect to Aβ1-42 peptide and its involvement in AD. However, the initial seed structure responsible for the Aβ1-42 peptide aggregation and the mechanism remains unclear. This may be chiefly attributed to the poor understanding of the processes involved in the Aβ1-42 peptide mis-folding and aggregation. Further, the flexibility and the aggregation propensity involved in the Aβ1-42 monomer, challenges the experimental and theoretical techniques to characterize the seed structure that drives the mis-folding and the subsequent aberrant aggregation. In this study, we employed all atoms fully unrestrained folding molecular dynamics simulation to identify the probable seed structure of Aβ1-42 peptide responsible for the aggregation. The initial linear structure of the Aβ1-42 peptide for the simulation was built from its amino acid sequence using leap module of AMBER. From our molecular dynamics study, we followed the secondary structure development in Aβ1-42 peptide starting from its initial linear structure to its folded 3D structure. We observed the Aβ1-42 peptide to sample diverse conformations which are rich in β-sheets and are stabilized by hydrogen bonding and other non-bonding interactions. The findings of this study shall be helpful in understanding the initial stage of Aβ1-42 peptide aggregation process and can be applicable for the development of therapeutics to cure AD at an early stage.

Keywords: Alzheimer's, AMBER, misfolding, protein aggregation.

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Article Details

Year: 2016
Published on: 31 August, 2016
Page: [172 - 178]
Pages: 7
DOI: 10.2174/1570164613999160831110617
Price: $25

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