Molecular Dynamics Simulations of Acetylcholinesterase – Beta-Amyloid Peptide Complex

Author:

Atanasova Mariana1,Dimitrov Ivan1,Ivanov Stefan12

Affiliation:

1. Faculty of Pharmacy , Medical University of Sofia , Sofia , Bulgaria

2. Institute for Bioscience and Biotechnology Research , University of Maryland , Rockville , MD 20850, USA

Abstract

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.

Publisher

Walter de Gruyter GmbH

Subject

General Computer Science

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