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.


Journal Details

This article was published in the following journal.

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


DeepDyve research library

PubMed Articles [18749 Associated PubMed Articles listed on BioPortfolio]

Targeting the relaxin/insulin-like family peptide receptor 1 and 2 with small molecule compounds.

The peptide hormone relaxin has beneficial roles in several organs through its action on its cognate G protein-coupled receptor, RXFP1. Relaxin administration is limited to intravenous, subcutaneous, ...

Fluorescent peptide displacement as a general assay for screening small molecule libraries against RNA.

A prominent hurdle in developing small molecule probes against RNA is the relative scarcity of general screening methods. In this study, we demonstrate the application of a fluorescent peptide displac...

Molecular docking, molecular dynamics simulations and QSAR studies on some of 2-arylethenylquinoline derivatives for inhibition of Alzheimer's amyloid-beta aggregation: Insight into mechanism of interactions and parameters for design of new inhibitors.

Alzheimer's disease is characterized using amyloid-beta (Aβ) aggregation. The present work was carried out to extend and design a novel quantitative structure-activity relationship (QSAR) model on in...

In silico modeling of Plasmodium falciparum chloroquine resistance transporter protein and biochemical studies suggest its key contribution to chloroquine resistance.

Chloroquine (CQ) has been used for decades as the primary chemotherapeutic drug for the treatment of malaria. The emergence of drug resistance in Plasmodium falciparum has been considered to be becaus...

Development of Inhibitors of the Programmed Cell Death-1/Programmed Cell Death-ligand 1 Signaling Pathway.

The clinical success of inhibitors targeting the PD-1/PD-L1 pathway has made this an active field in cancer immunotherapy. Currently, most drugs targeting this pathway are monoclonal antibodies. Small...

Clinical Trials [5988 Associated Clinical Trials listed on BioPortfolio]

CALR Exon 9 Mutant Peptide Vaccine to Patients With CALR-mutant Myeloproliferative Neoplasms

A phase-I-first in man study in patients with calreticulin(CALR)-mutant MPN by vaccinating with exon 9 mutated peptide with the adjuvant Montanide ISA-51 to monitor safety and toxicity and...

In Vivo IGF-1R Molecular Imaging Using [68Ga]- Labelling Anti-IGF-1R Affibody Molecule

The investigators developed [68Ga]-labelling Anti-IGF-1R Affibody Molecule as a targeted molecular imaging agent for noninvasive and repeatable detecting IGF-1R expression status.

A Multicenter, Double-Blind Study to Investigate the Safety and Efficacy of Arimoclomol in Volunteers With ALS

Arimoclomol is a small molecule that upregulates "molecular chaperones" in cells under stress. Arimoclomol extends survival by five weeks when given both pre-symptomatically and at disease...

Immunization of Patients With Metastatic Melanoma Using the GP100 Peptide Preceded by an Endoplasmic Reticulum Insertion Signal Sequence

Patients with metastatic melanoma who are HLA-A201+ will be immunized with a modified peptide from the gp100 molecule that contains a signal sequence designed to improve peptide presentati...

In Vivo EGFR-ECD Molecular Imaging Using [68Ga]- Labelling Anti-EGFR Affibody Molecule

The investigators developed [68Ga]-labelling Anti-EGFR Affibody Molecule as a targeted molecular imaging agent for noninvasive and repeatable detecting EGFR-ECD expression status.

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.

Quick Search


DeepDyve research library

Relevant Topics

Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...

Alzheimer's Disease
Of all the types of Dementia, Alzheimer's disease is the most common, affecting around 465,000 people in the UK. Neurons in the brain die, becuase  'plaques' and 'tangles' (mis-folded proteins) form in the brain. People with Al...

Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...

Searches Linking to this Article