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

Intrinsically Disordered Proteins02:18

Intrinsically Disordered Proteins

Intrinsically disordered proteins are a group of proteins that do not fold into specific three-dimensional structures. Their structural flexibility allows them to complement ordered proteins to perform functions that are inaccessible to rigid structures. They are more common in eukaryotes than prokaryotes and may either be exclusively intrinsically disordered or hybrid proteins, consisting of a mix of ordered and disordered regions. The absence of a rigid structure in these proteins can be...
Intrinsically Disordered Proteins02:18

Intrinsically Disordered Proteins

Intrinsically disordered proteins are a group of proteins that do not fold into specific three-dimensional structures. Their structural flexibility allows them to complement ordered proteins to perform functions that are inaccessible to rigid structures. They are more common in eukaryotes than prokaryotes and may either be exclusively intrinsically disordered or hybrid proteins, consisting of a mix of ordered and disordered regions. The absence of a rigid structure in these proteins can be...
Protein Folding01:22

Protein Folding

Overview
Protein Organization01:13

Protein Organization

Overview
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 can...
Electron Microscope Tomography and Single-particle Reconstruction01:07

Electron Microscope Tomography and Single-particle Reconstruction

Transmission electron microscopy (TEM) can be used to determine the 3D structure of biological samples with the help of techniques such as electron microscope tomography and single-particle reconstruction. While single-particle reconstruction can examine macromolecules and macromolecular complexes in vitro conditions only, tomography permits the study of cell components or small cells in vivo.
Electron Tomography
Electron tomography can be performed either in TEM or STEM (scanning transmission...

You might also read

Related Articles

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

Sort by
Same author

Proteome-scale quantification of the interactions driving condensate formation of intrinsically disordered proteins.

Nature communications·2026
Same author

Structures of protein folding intermediates on the ribosome.

Nature structural & molecular biology·2026
Same author

Integrated NMR/MD investigation reveals differences after reweighting in conformational ensembles of GAAG and GCAA tetraloops.

RNA (New York, N.Y.)·2026
Same author

Effects of residue substitutions on the cellular abundance of proteins.

eLife·2026
Same author

StruCloze: A Unified Framework for Backmapping and Inpainting Biomolecule Structures.

Journal of chemical theory and computation·2026
Same author

A Stickiness Scale for Disordered Proteins.

The journal of physical chemistry. B·2026

Related Experiment Video

Updated: May 15, 2026

Paramagnetic Relaxation Enhancement for Detecting and Characterizing Self-Associations of Intrinsically Disordered Proteins
07:24

Paramagnetic Relaxation Enhancement for Detecting and Characterizing Self-Associations of Intrinsically Disordered Proteins

Published on: September 23, 2021

Transient tertiary structure in intrinsically disordered proteins revealed by multithermal enhanced sampling.

Julian O Streit1,2, Michele Invernizzi3, Sandro Bottaro3

  • 1Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Copenhagen N, Denmark.

Nature Communications
|May 13, 2026
PubMed
Summary

On-the-fly Probability Enhanced Sampling (OPES) efficiently generates atomistic ensembles for intrinsically disordered proteins. This method accelerates discovery of rare, functionally important protein conformations, aiding drug design.

More Related Videos

NMR 15N Relaxation Experiments for the Investigation of Picosecond to Nanoseconds Structural Dynamics of Proteins
09:25

NMR 15N Relaxation Experiments for the Investigation of Picosecond to Nanoseconds Structural Dynamics of Proteins

Published on: November 1, 2024

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

Related Experiment Videos

Last Updated: May 15, 2026

Paramagnetic Relaxation Enhancement for Detecting and Characterizing Self-Associations of Intrinsically Disordered Proteins
07:24

Paramagnetic Relaxation Enhancement for Detecting and Characterizing Self-Associations of Intrinsically Disordered Proteins

Published on: September 23, 2021

NMR 15N Relaxation Experiments for the Investigation of Picosecond to Nanoseconds Structural Dynamics of Proteins
09:25

NMR 15N Relaxation Experiments for the Investigation of Picosecond to Nanoseconds Structural Dynamics of Proteins

Published on: November 1, 2024

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

Area of Science:

  • Computational Biology
  • Biophysics
  • Protein Dynamics

Background:

  • Intrinsically disordered proteins (IDPs) exhibit heterogeneous conformational ensembles.
  • Characterizing IDP dynamics is challenging due to sampling limitations in simulations.

Purpose of the Study:

  • To introduce and validate On-the-fly Probability Enhanced Sampling (OPES) for efficient IDP conformational sampling.
  • To explore the functional relevance of transiently structured states in IDPs.

Main Methods:

  • Utilized OPES in a multithermal ensemble for atomistic simulations of peptides and proteins (15-71 residues).
  • Employed OPES within a single replica, avoiding replica exchange and extensive parameter tuning.
  • Compared OPES results with replica-exchange with solute tempering (REST2) and unbiased simulations.

Main Results:

  • OPES efficiently generated atomistic ensembles for IDPs, accelerating convergence and exploring low-population states.
  • Simulations of the transcriptional coactivator ACTR revealed transiently folded alpha-helical states.
  • These states exhibited cooperative folding and tertiary contacts, consistent with NMR and SAXS data.

Conclusions:

  • OPES provides a robust and accessible method for sampling functionally relevant conformations in IDPs.
  • Transiently structured states in ACTR may facilitate folding-upon-binding via conformational selection.
  • These findings have implications for drug design and engineering of IDPs.