Related Experiment Video

Updated: Oct 19, 2025

High-Resolution Neutron Spectroscopy to Study Picosecond-Nanosecond Dynamics of Proteins and Hydration Water
08:48

High-Resolution Neutron Spectroscopy to Study Picosecond-Nanosecond Dynamics of Proteins and Hydration Water

Published on: April 28, 2022

1.9K

Molecular dynamics study of conformation transition from helix to sheet of Aβ42 peptide

Min Zhou1, Huilin Wen1, Huimin Lei2

  • 1School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, China.

Journal of Molecular Graphics & Modelling
|September 17, 2021
PubMed

Insights

Stabilizing the helical structure of amyloid-beta 42 (Aβ42) peptides in the Y10-A21 region can prevent their aggregation. This research clarifies the transition from helix to sheet structures, crucial for understanding neurotoxicity.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Neuroscience

Background:

  • Amyloid-beta 42 (Aβ42) peptides undergo conformational changes between alpha-helix and beta-sheet structures.
  • These conformational transitions are linked to Aβ42 aggregation and neurotoxicity, but the mechanism remains unclear.

Purpose of the Study:

  • To investigate the conformational transition of Aβ42 peptides from α-helix to β-sheet using molecular dynamics simulations.
  • To identify intermediate states and pathways involved in this transition.
  • To understand how Aβ42 conformation influences aggregation propensity.

Main Methods:

  • Microsecond timescale molecular dynamics (MD) simulations of Aβ42 peptides.
  • Construction of a Markov state model (MSM) to analyze conformational dynamics.
  • Simulation of Aβ42 peptide aggregation with different initial conformations.

Main Results:

  • The Y10-A21 region of Aβ42 is identified as critical for initiating the helix-to-sheet transition.
  • Collapse of the helical structure in the Y10-A21 region may trigger β-sheet formation.
  • Aβ42 peptides in sheet conformation exhibit higher aggregation potential than those in helix conformation.

Conclusions:

  • Stabilizing the α-helix structure in the Y10-A21 region of Aβ42 can inhibit peptide aggregation.
  • This study provides insights into the conformational dynamics and aggregation mechanisms of Aβ42 peptides.
  • Findings may inform strategies for preventing Aβ42-related neurotoxicity.
Keywords:
AggregationAβ42 peptidesConformation transitionMSMTransition pathway

More Related Videos

Synthesis and Characterization of 1,2-Dithiolane Modified Self-Assembling Peptides09:54

Synthesis and Characterization of 1,2-Dithiolane Modified Self-Assembling Peptides

Published on: August 20, 2018

7.4K
Characterization of pH-Dependent Reversible Self-Assembly of Amyloid Beta 1-40-Coated Gold Colloids08:53

Characterization of pH-Dependent Reversible Self-Assembly of Amyloid Beta 1-40-Coated Gold Colloids

Published on: March 21, 2025

933

Related Concept Videos

Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
18.7K
Protein Folding01:25

Protein Folding

Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
9.7K
Protein and Protein Structure02:15

Protein and Protein Structure

Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme...
83.4K
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining,...
10.8K
Protein Organization01:13

Protein Organization

Overview
150.1K
¹H NMR of Conformationally Flexible Molecules: Temporal Resolution00:52

¹H NMR of Conformationally Flexible Molecules: Temporal Resolution

At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately 105 times per second. These two chair conformers are in equilibrium. The rapid ring flipping results in the interconversion of the axial proton to an equatorial proton and an equatorial to the axial proton. Such interconversions are too rapid and cannot be detected on the NMR timescale. Hence, the NMR spectrometer cannot distinguish between the...
958