<abstract xmlns="http://www.w3.org/1999/xhtml"><p>Alzheimer’s Disease (AD) is a neurodegenerative disorder with severe consequences and lethal outcome. One of the pathological hallmarks of the disease is the formation of insoluble intercellular beta-Amyloid (Aβ) plaques. The enzyme ACetylcholinEsterase (AChE) promotes and accelerates the aggregation of toxic Aβ protofibrils progressively converted into plaques. The Peripheral Anionic Site (PAS), part of the binding gorge of AChE, is one of the nucleation centers implicated in the Aβ aggregation. In this study, the Aβ peptide was docked into the PAS and the stability of the formed complex was investigated by molecular dynamics simulation for 1 μs (1000 ns). The complex was stable during the simulation. Apart from PAS, the Aβ peptide makes several additional contacts with AChE. The main residence area of Aβ on the surface of AChE is the region 344-361. This region is next to PAS but far enough to be sterically hindered by dual-site binding AChE inhibitors.</p></abstract>

Alzheimer’s Disease (AD) is a neurodegenerative disorder with severe consequences and lethal outcome. One of the pathological hallmarks of the disease is the formation of insoluble intercellular beta-Amyloid (Aβ) plaques. The enzyme ACetylcholinEsterase (AChE) promotes and accelerates the aggregation of toxic Aβ protofibrils progressively converted into plaques. The Peripheral Anionic Site (PAS), part of the binding gorge of AChE, is one of the nucleation centers implicated in the Aβ aggregation. In this study, the Aβ peptide was docked into the PAS and the stability of the formed complex was investigated by molecular dynamics simulation for 1 μs (1000 ns). The complex was stable during the simulation. Apart from PAS, the Aβ peptide makes several additional contacts with AChE. The main residence area of Aβ on the surface of AChE is the region 344-361. This region is next to PAS but far enough to be sterically hindered by dual-site binding AChE inhibitors.

Molecular Dynamics Simulations of Acetylcholinesterase – Beta-Amyloid Peptide Complex

Cybernetics and Information Technologies

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Alzheimer’s Disease (AD) is a neurodegenerative disorder with severe consequences and lethal outcome. One of the pathological hallmarks of the disease is the...

Molecular Dynamics Simulations of Acetylcholinesterase – Beta-Amyloid Peptide Complex

Published Online: Dec 31, 2020

Page range: 140 - 154

Received: Sep 15, 2020

Accepted: Oct 30, 2020

DOI: https://doi.org/10.2478/cait-2020-0068

Keywords
Alzheimer’s disease, beta-Amyloid (Aβ), acetylcholinesterase (AChE), Peripheral Anionic Site (PAS), Aβ aggregation, senile plaques, amyloid fibrils, neurodegenerative disorder, molecular dynamics

© 2020 Mariana Atanasova et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Molecular Dynamics Simulations of Acetylcholinesterase – Beta-Amyloid Peptide Complex

Published Online: Dec 31, 2020

Page range: 140 - 154

Received: Sep 15, 2020

Accepted: Oct 30, 2020

DOI: https://doi.org/10.2478/cait-2020-0068

KeywordsAlzheimer’s disease, beta-Amyloid (Aβ), acetylcholinesterase (AChE), Peripheral Anionic Site (PAS), Aβ aggregation, senile plaques, amyloid fibrils, neurodegenerative disorder, molecular dynamics

© 2020 Mariana Atanasova et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Keywords
Alzheimer’s disease, beta-Amyloid (Aβ), acetylcholinesterase (AChE), Peripheral Anionic Site (PAS), Aβ aggregation, senile plaques, amyloid fibrils, neurodegenerative disorder, molecular dynamics