文章基本信息

标题：Molecular Dynamics Simulations of Acetylcholinesterase - Beta-Amyloid Peptide Complex
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作者：Mariana Atanasova ; Ivan Dimitrov ; Stefan Ivanov 等
期刊名称：Cybernetics and Information Technologies
印刷版ISSN：1311-9702
电子版ISSN：1314-4081
出版年度：2020
卷号：20
期号：6
页码：140-154
DOI：10.2478/cait-2020-0068
语种：English
出版社：Bulgarian Academy of Science
摘要：Alzheimer’s Disease (AD) is a neurodegenerative disorder with severeconsequences and lethal outcome. One of the pathological hallmarks of the diseaseis the formation of insoluble intercellular beta-Amyloid (Aβ) plaques. The enzymeACetylcholinEsterase (AChE) promotes and accelerates the aggregation of toxic Aβprotofibrils progressively converted into plaques. The Peripheral Anionic Site (PAS),part of the binding gorge of AChE, is one of the nucleation centers implicated in theAβ aggregation. In this study, the Aβ peptide was docked into the PAS and thestability of the formed complex was investigated by molecular dynamics simulationfor 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 residencearea of Aβ on the surface of AChE is the region 344-361. This region is next to PASbut far enough to be sterically hindered by dual-site binding AChE inhibitors.
关键词：Alzheimer’s disease; beta-Amyloid (Aβ); acetylcholinesterase (AChE);Peripheral Anionic Site (PAS); Aβ aggregation; senile plaques; amyloid fibrils;neurodegenerative disorder; molecular dynamics.