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

17.7K
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...
17.7K
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

5.7K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.7K
Protein-protein Interfaces02:04

Protein-protein Interfaces

12.4K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
12.4K
Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

2.5K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.5K
Protein-Protein Interfaces02:04

Protein-Protein Interfaces

3.6K
3.6K
Conserved Binding Sites01:49

Conserved Binding Sites

4.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.2K

You might also read

Related Articles

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

Sort by
Same author

Structure-Based Experimental Datasets for Benchmarking Protein Simulation Force Fields [Article v1.0].

Living journal of computational molecular science·2026
Same author

How small molecules stabilize oligomers of a phase-separating disordered protein.

bioRxiv : the preprint server for biology·2025
Same author

Characterizing Structural and Kinetic Ensembles of Intrinsically Disordered Proteins Using Writhe.

Journal of chemical theory and computation·2025
Same author

Determining accurate conformational ensembles of intrinsically disordered proteins at atomic resolution.

Nature communications·2025
Same author

Monomer binding modes of small molecules that modulate the kinetics of hIAPP amyloid formation.

bioRxiv : the preprint server for biology·2025
Same author

Ensemble Docking for Intrinsically Disordered Proteins.

Journal of chemical information and modeling·2025
Same journal

Layered social competition coordinates reproductive hierarchy formation in ants.

bioRxiv : the preprint server for biology·2026
Same journal

Combination epigenetic-targeted therapy increases the immunogenicity of poorly immunogenic sarcomas.

bioRxiv : the preprint server for biology·2026
Same journal

Loss of LanC-like proteins delays post-injury regeneration of aging skeletal muscles.

bioRxiv : the preprint server for biology·2026
Same journal

Integrative Transfer Network: Deep Transfer Learning Across Populations and Prediction Targets.

bioRxiv : the preprint server for biology·2026
Same journal

Confidence-supported label-free metabolic imaging with FPhaS phase autofluorescence microscopy.

bioRxiv : the preprint server for biology·2026
Same journal

Sequence-encoded autoinhibition couples mRNA decapping activity to phase separation.

bioRxiv : the preprint server for biology·2026
See all related articles

Related Experiment Video

Updated: May 29, 2025

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

11.3K

Ensemble docking for intrinsically disordered proteins.

Anjali Dhar1, Thomas R Sisk1, Paul Robustelli1

  • 1Dartmouth College, Department of Chemistry, Hanover, NH, 03755.

Biorxiv : the Preprint Server for Biology
|February 3, 2025
PubMed
Summary
This summary is machine-generated.

Intrinsically disordered proteins (IDPs) are key drug targets, but challenging for traditional design. New ensemble docking methods accurately predict small molecule binding affinities and mechanisms for IDPs like alpha-synuclein.

Keywords:
Drug DiscoveryEnsemble dockingIntrinsically Disordered ProteinsMolecular DockingMolecular Dynamics

More Related Videos

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
10:58

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Published on: July 25, 2013

17.0K
Author Spotlight: Streamlining Protein Target Prediction and Validation via Molecular Docking and CETSA
10:21

Author Spotlight: Streamlining Protein Target Prediction and Validation via Molecular Docking and CETSA

Published on: February 23, 2024

2.3K

Related Experiment Videos

Last Updated: May 29, 2025

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

11.3K
Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
10:58

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Published on: July 25, 2013

17.0K
Author Spotlight: Streamlining Protein Target Prediction and Validation via Molecular Docking and CETSA
10:21

Author Spotlight: Streamlining Protein Target Prediction and Validation via Molecular Docking and CETSA

Published on: February 23, 2024

2.3K

Area of Science:

  • Biochemistry
  • Computational Biology
  • Drug Discovery

Background:

  • Intrinsically disordered proteins (IDPs) are linked to numerous human diseases.
  • IDPs lack stable 3D structures, making them difficult targets for conventional structure-based drug design.
  • Targeting IDPs offers a promising avenue for novel therapeutic strategies.

Purpose of the Study:

  • To develop computationally efficient ensemble docking approaches for predicting small molecule binding to IDPs.
  • To characterize the dynamic and heterogeneous binding mechanisms of small molecules with IDPs at atomic resolution.
  • To validate the predictive power of ensemble docking against experimental data.

Main Methods:

  • Development of ensemble docking protocols tailored for intrinsically disordered proteins.
  • Application of methods to predict relative binding affinities of small molecule ligands.
  • Utilizing NMR spectroscopy for experimental validation of binding affinities.
  • Comparison with long-timescale molecular dynamics simulations for binding mode analysis.

Main Results:

  • Ensemble docking accurately predicted the relative binding affinities of alpha-synuclein ligands.
  • The computational method generated conformational ensembles of ligand binding modes.
  • Results showed remarkable agreement with experimentally validated molecular dynamics simulations.
  • Demonstrated the capability to characterize dynamic binding mechanisms at atomic resolution.

Conclusions:

  • Ensemble docking approaches show significant potential for predicting small molecule binding to IDPs.
  • These computational methods can effectively characterize dynamic and heterogeneous binding mechanisms.
  • The developed protocols may serve as valuable tools for accelerating IDP drug discovery campaigns.