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

Protein Folding01:25

Protein Folding

9.9K
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...
9.9K
Protein Folding01:22

Protein Folding

124.2K
Overview
124.2K
Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

18.9K
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...
18.9K
Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

14.0K
14.0K
Protein Organization01:13

Protein Organization

151.6K
Overview
151.6K
Protein Organization01:24

Protein Organization

8.2K
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence....
8.2K

You might also read

Related Articles

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

Sort by
Same author

The master molecule that built biology: How water shaped the chemistry of life.

Protein science : a publication of the Protein Society·2026
Same author

50 years in the shadow of the Ramachandran plot.

Protein science : a publication of the Protein Society·2025
Same author

From propensities to patterns to principles in protein folding.

Proteins·2023
Same author

Opinion: Protein folds vs. protein folding: Differing questions, different challenges.

Proceedings of the National Academy of Sciences of the United States of America·2022
Same author

Reframing the Protein Folding Problem: Entropy as Organizer.

Biochemistry·2021
Same author

Ramachandran maps for side chains in globular proteins.

Proteins·2019
Same journal

Macromolecular crowding inhibits degradation of alpha-synuclein amyloid fibrils induced by cathepsins and MMP9.

Protein science : a publication of the Protein Society·2026
Same journal

Sequence-encoded differences in the conformational ensembles of CITED transcriptional activation domains impact coactivator binding.

Protein science : a publication of the Protein Society·2026
Same journal

The phospholipid biosynthesis enzyme PlsB contains three distinct domains for membrane association, lysophosphatidic acid synthesis, and dimerization.

Protein science : a publication of the Protein Society·2026
Same journal

Structural basis of ligand selectivity in FAD/NAD(P)H-dependent dehydrogenases: insights from trypanothione reductase and type II NADH dehydrogenase.

Protein science : a publication of the Protein Society·2026
Same journal

Achieving protease substrate-specific inhibition by mAb dual functional selections.

Protein science : a publication of the Protein Society·2026
Same journal

How important are quantum mechanical effects in controlling biological functions: Enzymes, electron transfer and bird navigation.

Protein science : a publication of the Protein Society·2026
See all related articles

Related Experiment Video

Updated: Nov 7, 2025

Microfluidic Mixers for Studying Protein Folding
12:42

Microfluidic Mixers for Studying Protein Folding

Published on: April 10, 2012

15.3K

Protein folding - seeing is deceiving.

George D Rose1

  • 1T.C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, Maryland, USA.

Protein Science : a Publication of the Protein Society
|May 3, 2021
PubMed
Summary
This summary is machine-generated.

Protein folding may be driven by unfavorable interactions excluding non-native states, rather than solely by favorable interactions forming the native state. Hydrogen bond satisfaction is key to resolving protein folding paradoxes.

Keywords:
Levinthal paradoxbackbone-based modelconformational entropyexcluding interactionshydrogen-bond satisfactionprotein foldingsteric clash

More Related Videos

Thermodynamics of Membrane Protein Folding Measured by Fluorescence Spectroscopy
10:09

Thermodynamics of Membrane Protein Folding Measured by Fluorescence Spectroscopy

Published on: April 28, 2011

18.6K
4D Imaging of Protein Aggregation in Live Cells
08:59

4D Imaging of Protein Aggregation in Live Cells

Published on: April 5, 2013

17.6K

Related Experiment Videos

Last Updated: Nov 7, 2025

Microfluidic Mixers for Studying Protein Folding
12:42

Microfluidic Mixers for Studying Protein Folding

Published on: April 10, 2012

15.3K
Thermodynamics of Membrane Protein Folding Measured by Fluorescence Spectroscopy
10:09

Thermodynamics of Membrane Protein Folding Measured by Fluorescence Spectroscopy

Published on: April 28, 2011

18.6K
4D Imaging of Protein Aggregation in Live Cells
08:59

4D Imaging of Protein Aggregation in Live Cells

Published on: April 5, 2013

17.6K

Area of Science:

  • Biochemistry
  • Structural Biology
  • Computational Biology

Background:

  • The conventional model of protein folding posits a vast conformational space under unfolding conditions, collapsing to a single native state under folding conditions, involving significant conformational entropy loss.
  • This entropy loss is traditionally explained by favorable side-chain interactions compensating for it and dictating native structure.

Purpose of the Study:

  • To challenge the conventional interpretation of protein folding by proposing an alternative mechanism.
  • To introduce the concept of high-energy excluding interactions as a primary driver of protein folding.

Main Methods:

  • The perspective proposes that unfavorable excluding interactions (steric clash, unsatisfied hydrogen bonds) significantly reduce the accessible conformational population under folding conditions.
  • It highlights the role of solvent factors in promoting compactness and the inherent properties of secondary structures (alpha-helices, beta-sheets) that balance hydrogen bonds and avoid steric clashes.

Main Results:

  • Excluding interactions, alongside solvent effects, promote substantial protein chain organization.
  • Proteins' secondary structural elements are uniquely suited to satisfy hydrogen bonds and avoid steric clashes, limiting fundamental folds to approximately 10,000 per domain.
  • Accounting for excluding interactions resolves the protein "frustration" problem and the Levinthal paradox.

Conclusions:

  • Hydrogen bond satisfaction is likely an underappreciated yet critical parameter in protein folding models.
  • This perspective suggests a shift from viewing folding as solely driven by favorable interactions to one where unfavorable interactions play a crucial winnowing role.