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 Experiment Videos

Fast-folding protein kinetics, hidden intermediates, and the sequential stabilization model.

S Banu Ozkan1, Ken A Dill, Ivet Bahar

  • 1Center for Computational Biology and Bioinformatics, and Department of Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh, Pennsylvania 15213, USA.

Protein Science : a Publication of the Protein Society
|July 27, 2002
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

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

Sort by
Same author

DruGUI 2.0: mapping protein druggability with probe-based molecular dynamics.

Bioinformatics (Oxford, England)·2026
Same author

15-LOX-catalytic bias towards ether-(alkenyl)-ETE-PEs oxidation bestows selectivity of PRO-ferroptotic cell death signaling.

Nature communications·2026
Same author

Structural and molecular determinants of glutamate transporter allosteric modulators.

Molecular pharmacology·2026
Same author

Small Molecule Activators of Protein Phosphatase 2A Exert Global Stabilizing Effects on the Scaffold PR65.

JACS Au·2026
Same author

Cryo-electron microscopy structure of a zinc uptake ABC transporter.

Structure (London, England : 1993)·2026
Same author

Nonequilibrium Theory for Molecular Machine Design.

ArXiv·2026

Protein folding may involve parallel pathways, not just single routes. This study reveals hidden intermediates and complex funnel landscapes consistent with multiple folding trajectories, challenging previous interpretations.

Area of Science:

  • Biophysics
  • Computational Biology
  • Protein Dynamics

Background:

  • Native-state hydrogen exchange experiments reveal discrete nonnative structures in equilibrium with the native state, termed hidden intermediates (HIs).
  • HIs have been interpreted as evidence against protein folding funnel models, suggesting discrete pathways rather than continuous landscapes.
  • Funnel models traditionally imply a lack of specific folding sequences, a continuum of structures, and smooth energy landscapes.

Purpose of the Study:

  • To investigate the consistency of microscopic protein folding models with the existence of hidden intermediates.
  • To determine whether protein folding occurs via single pathways or multiple, parallel routes.
  • To analyze the energy landscape of protein folding using computational dynamics.

Main Methods:

Related Experiment Videos

  • Exact dynamics of a simplified microscopic model were solved.
  • Singular value decomposition was employed to analyze model energy landscapes.
  • Comparison of simulation results with experimental observations of hidden intermediates and kinetic experiments.

Main Results:

  • The microscopic model is consistent with the presence of hidden intermediates and transition states.
  • These states were found to occur in parallel pathways, not a single sequential pathway.
  • A high multiplicity of microscopic folding trajectories was observed, resolving into two macroscopic pathways.
  • Complex funnel-shaped energy landscapes were accurately represented.

Conclusions:

  • Protein folding can be consistent with hidden intermediates and parallel pathways.
  • The traditional view of a single reaction coordinate for folding may be an oversimplification.
  • Macroscopic observations of protein folding can emerge from a complex, multi-trajectory microscopic landscape.