Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Amyloid Fibrils03:03

Amyloid Fibrils

9.5K
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,...
9.5K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Temperature-Dependent Dynamics of Aβ42 and α-Synuclein Monomers and Early Oligomerization of Aβ42: Shared Residues Mediate Intra- and Intermolecular β-Sheets.

ACS chemical neuroscience·2026
Same author

Protein Recognition of Linear and Cyclic Peptides of Homologous Sequences Implicated in the Aggregation of α-Synuclein.

The journal of physical chemistry. B·2025
Same author

Membrane Permeability of Cyclic and Linear Peptides, a Halogenated Antisickling Molecule, and Water Across a Red Blood Cell Bilayer Model.

The journal of physical chemistry letters·2025
Same author

Sickle Cell Hemoglobin "Drugged" with Cyclic Peptides Is Aggregation Incompetent.

The journal of physical chemistry. B·2024
Same author

Essential dynamics of ubiquitin in water and in a natural deep eutectic solvent.

Physical chemistry chemical physics : PCCP·2024
Same author

Protein stability in a natural deep eutectic solvent: Preferential hydration or solvent slaving?

The Journal of chemical physics·2023

Related Experiment Video

Updated: Jun 19, 2025

Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry for the Study of Alpha-Synuclein Structural Dynamics Under Physiological Conditions
08:40

Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry for the Study of Alpha-Synuclein Structural Dynamics Under Physiological Conditions

Published on: June 23, 2022

2.9K

Wild-Type α-Synuclein Structure and Aggregation: A Comprehensive Coarse-Grained and All-Atom Molecular Dynamics

Gabriel F Martins1, Nuno Galamba1

  • 1BioISI─Biosystems and Integrative Sciences Institute, Faculty of Sciences of the University of Lisbon, C8, Campo Grande, 1749-016 Lisbon, Portugal.

Journal of Chemical Information and Modeling
|July 24, 2024
PubMed
Summary

Coarse-grained models for alpha-synuclein (α-syn) show significant differences in aggregation behavior. The Sirah2 model, with specific enhancements, accurately simulates α-syn aggregation relevant to Parkinson's disease drug discovery.

More Related Videos

Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time
07:56

Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time

Published on: May 30, 2021

3.2K
Studying Pre-formed Fibril Induced α-Synuclein Accumulation in Primary Embryonic Mouse Midbrain Dopamine Neurons
10:03

Studying Pre-formed Fibril Induced α-Synuclein Accumulation in Primary Embryonic Mouse Midbrain Dopamine Neurons

Published on: August 16, 2020

10.6K

Related Experiment Videos

Last Updated: Jun 19, 2025

Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry for the Study of Alpha-Synuclein Structural Dynamics Under Physiological Conditions
08:40

Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry for the Study of Alpha-Synuclein Structural Dynamics Under Physiological Conditions

Published on: June 23, 2022

2.9K
Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time
07:56

Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time

Published on: May 30, 2021

3.2K
Studying Pre-formed Fibril Induced α-Synuclein Accumulation in Primary Embryonic Mouse Midbrain Dopamine Neurons
10:03

Studying Pre-formed Fibril Induced α-Synuclein Accumulation in Primary Embryonic Mouse Midbrain Dopamine Neurons

Published on: August 16, 2020

10.6K

Area of Science:

  • Biophysics
  • Computational Biology
  • Neuroscience

Background:

  • Alpha-synuclein (α-syn) is intrinsically disordered and central to Parkinson's disease pathogenesis.
  • Accurately simulating α-syn structure and aggregation is crucial for understanding Parkinson's disease and developing therapies.
  • Coarse-grained (CG) force fields offer a computationally efficient alternative to all-atom simulations for large intrinsically disordered proteins (IDPs).

Purpose of the Study:

  • To compare the accuracy of different coarse-grained (CG) force fields (Martini3, Sirah2) and all-atom (AA) force fields (Amber99sb, Charmm36m) in simulating α-syn structure and aggregation.
  • To investigate the impact of protein-water interactions and enhanced sampling methods on CG simulations of α-syn.
  • To evaluate the stability of CG α-syn fibrils and the aggregation propensity of the NACore peptide.

Main Methods:

  • Molecular dynamics simulations using Martini3, Sirah2, Amber99sb, and Charmm36m force fields.
  • Analysis of α-syn monomer structure, dynamics, and fibril stability.
  • Umbrella sampling simulations to calculate free energy profiles for α-syn and NACore peptide aggregation.
  • Investigation of protein-water interactions and the necessity of enhanced sampling techniques.

Main Results:

  • While Martini3 and Sirah2 models show similar α-syn monomer structures, they exhibit significant differences in aggregation behavior.
  • The Martini3 fibril model proved unstable, and its binding free energy for α-syn and NACore was positive.
  • Sirah2, particularly with enhanced protein-water interactions and neutral termini, demonstrated stable aggregation and provided free energy profiles comparable to all-atom models.

Conclusions:

  • The choice of CG force field significantly impacts the simulation of α-syn aggregation.
  • Sirah2, with optimized parameters for protein-water interactions and termini, is a suitable CG model for studying α-syn protein-protein and protein-drug interactions.
  • Accurate simulation of α-syn aggregation using CG models holds promise for advancing Parkinson's disease research and therapeutic development.