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Specific interaction from different Aβ42 peptide fragments to α7nAChR-A study of molecular dynamics simulation.

Authors :
Gao, Xvzhi
Guan, Yvning
Wang, Chuanbo
Jia, Mengke
Ahmad, Sajjad
Nouman, Muhammad Fahad
Ai, Hongqi
Source :
Journal of Molecular Modeling; Jul2024, Vol. 30 Issue 7, p1-9, 9p
Publication Year :
2024

Abstract

Context: Existing researches confirmed that β amyloid (Aβ) has a high affinity for the α7 nicotinic acetylcholine receptor (α7nAChR), associating closely to Alzheimer's disease. The majority of related studies focused on the experimental reports on the neuroprotective role of Aβ fragment (Aβ<subscript>x</subscript>), however, with a lack of investigation into the most suitable binding region and mechanism of action between Aβ fragment and α7nAChR. In the study, we employed four Aβ<subscript>1–42</subscript> fragments Aβ<subscript>x</subscript>, Aβ<subscript>1–16</subscript>, Aβ<subscript>10–16</subscript>, Aβ<subscript>12–28</subscript>, and Aβ<subscript>30–42</subscript>, of which the first three were confirmed to play neuroprotective roles upon directly binding, to interact with α7nAChR. Methods: The protein–ligand docking server of CABS-DOCK was employed to obtain the α7nAChR-Aβ<subscript>x</subscript> complexes. Only the top α7nAChR-Aβ<subscript>x</subscript> complexes were used to perform all-atom GROMACS dynamics simulation in combination with Charmm36 force field, by which α7nAChR-Aβ<subscript>x</subscript> interactions' dynamic behavior and specific locations of these different Aβ<subscript>x</subscript> fragments were identified. MM-PBSA calculations were also done to estimate the binding free energies and the different contributions from the residues in the Aβ<subscript>x</subscript>. Two distinct results for the first three and fourth Aβ<subscript>x</subscript> fragments in binding site, strength, key residue, and orientation, account for why the fourth fails to play a neuroprotective role at the molecular level. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
16102940
Volume :
30
Issue :
7
Database :
Complementary Index
Journal :
Journal of Molecular Modeling
Publication Type :
Academic Journal
Accession number :
178528657
Full Text :
https://doi.org/10.1007/s00894-024-06032-w