Molecular Dynamics Simulations of Acetylcholinesterase - Beta-Amyloid Peptide Complex

被引：1

作者：

Atanasova, Mariana ^{[1
]}

Dimitrov, Ivan ^{[1
]}

Ivanov, Stefan ^{[1
,2
]}

机构：

[1] Med Univ Sofia, Fac Pharm, Sofia, Bulgaria

[2] Univ Maryland, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA

来源：

CYBERNETICS AND INFORMATION TECHNOLOGIES | 2020年 / 20卷 / 06期

关键词：

Alzheimer's disease; beta-Amyloid (A beta); acetylcholinesterase (AChE); Peripheral Anionic Site (PAS); A beta aggregation; senile plaques; amyloid fibrils; neurodegenerative disorder; molecular dynamics; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; MOUSE MODEL; A-BETA; AGGREGATION; PROTEIN; DEPOSITION; CHOLINESTERASES; FIBRILS; CHAIN;

D O I：

10.2478/cait-2020-0068

中图分类号：

TP [自动化技术、计算机技术];

学科分类号：

0812 ;

摘要：

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 (A beta) plaques. The enzyme ACetylcholinEsterase (AChE) promotes and accelerates the aggregation of toxic A beta 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 A beta aggregation. In this study, the A beta peptide was docked into the PAS and the stability of the formed complex was investigated by molecular dynamics simulation for 1 mu s (1000 ns). The complex was stable during the simulation. Apart from PAS, the A beta peptide makes several additional contacts with AChE. The main residence area of A beta 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.

引用

页码：140 / 154

页数：15

共 52 条

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