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Related Concept Videos

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...
Protein Folding01:22

Protein Folding

Overview
Protein Folding01:22

Protein Folding

Overview
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...
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...
Protein Organization01:13

Protein Organization

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Related Experiment Video

Updated: Jun 23, 2026

Microfluidic Mixers for Studying Protein Folding
12:42

Microfluidic Mixers for Studying Protein Folding

Published on: April 10, 2012

Many Ways Out: Beyond the Two-State Model of Protein Unfolding.

Annalisa Pastore1,2,3, Piero Andrea Temussi4

  • 1Department of Clinical and Basic Neurosciences, King's College London, SW59RT London, U.K.

ACS Omega
|June 22, 2026
PubMed
Summary

Protein unfolding is more complex than a simple two-state transition. The unfolded state is a dynamic ensemble, and intermediate conformations are often sampled during the unfolding process.

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Last Updated: Jun 23, 2026

Microfluidic Mixers for Studying Protein Folding
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Published on: April 10, 2012

NMR 15N Relaxation Experiments for the Investigation of Picosecond to Nanoseconds Structural Dynamics of Proteins
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Published on: November 1, 2024

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09:51

Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web

Published on: July 16, 2017

Area of Science:

  • Biochemistry
  • Structural Biology
  • Protein Dynamics

Background:

  • The traditional view of protein unfolding involves a transition between a single folded state and a single unfolded state.
  • Emerging evidence suggests a more complex scenario involving a conformational ensemble in the unfolded state.
  • Understanding protein unfolding is crucial for comprehending protein stability and function.

Purpose of the Study:

  • To critically re-examine the traditional two-state model of protein unfolding.
  • To explore the concept of a complex, heterogeneous unfolded state.
  • To discuss the implications of intermediate conformations during protein unfolding.

Main Methods:

  • Review of existing literature on protein stability and unfolding.
  • Analysis of experimental and theoretical data supporting complex unfolding pathways.
  • Critical evaluation of the limitations of the two-state model.

Main Results:

  • The unfolded state is best described as a conformational ensemble, not a single form.
  • Proteins can sample intermediate conformations with residual secondary structures or partially preserved hydrophobic cores.
  • Minor transitions involving local secondary structures occur during unfolding.
  • Low-populated intermediates may exist but are often undetected.

Conclusions:

  • The two-state model is an oversimplification of protein unfolding.
  • A more nuanced understanding of protein unfolding pathways and the nature of the unfolded state is required.
  • Further research is needed to fully characterize the conformational landscape of unfolded proteins.