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Molecular docking of Aβ peptide and its Iowa DN mutant using small molecule inhibitors: Possible mechanisms of Aβ-peptide inhibition.

07:00 EST 4th January 2019 | BioPortfolio

Summary of "Molecular docking of Aβ peptide and its Iowa DN mutant using small molecule inhibitors: Possible mechanisms of Aβ-peptide inhibition."

Alzheimer's disease (AD) is the most common form of neurodegenerative diseases, characterized by the deposition of Aβ (amyloid beta) peptide. In this study, we have unravelled the interactions as well as anti amyloidogenic behaviour of 40 small molecule inhibitors with Aβ peptide and Iowa mutant DN-Aβ1 peptide at atomic level and their modes of binding by docking approaches. The binding mode between wild type peptide and drug is distinctly different from the Iowa-mutant-peptide and drug. Here we proposed possible mechanisms of amyloid beta peptide inhibition by small molecule and prevent monomer-monomer interactions via at least three different mechanisms. In the first mechanism, four catechins efficiently interacted with the C-terminal region of peptides through hydrogen bonds and inhibited the peptides. This may lead to blockage of access of second molecule of Aβ-peptide. Secondly, in the case Iowa mutant D23N-Aβ peptide, same catechin form hydrogen bond with the important mutated Asn residue which acts as hydrogen bond donor and acceptor leading to tight binding of inhibitor with the peptide and may prevent monomer-monomer interactions. The third mechanism relies on the ability of drug molecules to mask hydrophobic residues of the peptide, thereby possibly inhibiting hydrophobic interactions between the two beta peptides.

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This article was published in the following journal.

Name: International journal of biological macromolecules
ISSN: 1879-0003
Pages:

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Medical and Biotech [MESH] Definitions

A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein.

Large collections of small molecules (molecular weight about 600 or less), of similar or diverse nature which are used for high-throughput screening analysis of the gene function, protein interaction, cellular processing, biochemical pathways, or other chemical interactions.

Part of a MESSENGER RNA molecule that undergoes a conformation change upon binding a specific metabolite or other small molecule thereby regulating the messenger RNA's transcription, post-transcriptional processing, transport, translation, or stability in response to varying levels of the metabolite or other small molecule.

A 36-amino acid peptide produced by the L cells of the distal small intestine and colon. Peptide YY inhibits gastric and pancreatic secretion.

State bounded on the north by Lake Superior and Michigan, on the east by Lake Michigan, on the south by Illinois and Iowa, and on the west by Minnesota and Iowa.

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