Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Intrinsically Disordered Proteins

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...

You might also read

Related Articles

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

Sort by

Same author

Reversible molecular simulation for training classical and machine-learning force fields.

Proceedings of the National Academy of Sciences of the United States of America·2025

Same author

Fast protein structure searching using structure graph embeddings.

Bioinformatics advances·2025

Same author

A guide to machine learning for biologists.

Nature reviews. Molecular cell biology·2021

Same author

Differentiable molecular simulation can learn all the parameters in a coarse-grained force field for proteins.

PloS one·2021

Same journal

Tunable redox hopping charge transport and electrochromism in multivariate MOFs: effects of substitution patterns and number of sulfonic acid groups.

Chemical science·2026

Same journal

Dearomative [2 + 2] photocycloaddition to difluoro bicyclo[2.1.1]hexane bioisosteres.

Chemical science·2026

Same journal

Chemoproteomics unveils the antibacterial mechanism of silver ions: inhibiting peptidoglycan synthesis <i>via</i> targeting Mur family proteins in <i>Staphylococcus aureus</i>.

Chemical science·2026

Same journal

PFAS free chemically amplified resists enabled by low activation energy hydrocarbon cage monomers.

Chemical science·2026

Same journal

Membrane anchoring amplifies intracellular catalysis of caged palladium nanoclusters.

Chemical science·2026

Same journal

Bistelluridopnictanes as gateways to telluradipnictiranes and a cyclic [Bi<sub>2</sub>Te<sub>2</sub>]<sup>2+</sup> dication.

Chemical science·2026

See all related articles

Search research articles

Related Experiment Video

Updated: Jun 29, 2025

Author Spotlight: Advancing Cell Membrane Biophysics - Exploring Interactions and Challenges Through Experimental and Computational Approaches

Author Spotlight: Advancing Cell Membrane Biophysics - Exploring Interactions and Challenges Through Experimental and Computational Approaches

Published on: September 1, 2023

Differentiable simulation to develop molecular dynamics force fields for disordered proteins.

Joe G Greener¹

¹Medical Research Council Laboratory of Molecular Biology Cambridge CB2 0QH UK jgreener@mrc-lmb.cam.ac.uk.

Chemical Science

|March 29, 2024

Summary

This summary is machine-generated.

This study enhances implicit solvent force fields for disordered proteins using differentiable simulations. The new GB99dms model improves accuracy for intrinsically disordered proteins while maintaining performance for folded proteins.

More Related Videos

Structure-Based Simulation and Sampling of Transcription Factor Protein Movements along DNA from Atomic-Scale Stepping to Coarse-Grained Diffusion

Structure-Based Simulation and Sampling of Transcription Factor Protein Movements along DNA from Atomic-Scale Stepping to Coarse-Grained Diffusion

Published on: March 1, 2022

Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function

Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function

Published on: April 26, 2024

Related Experiment Videos

Last Updated: Jun 29, 2025

Author Spotlight: Advancing Cell Membrane Biophysics - Exploring Interactions and Challenges Through Experimental and Computational Approaches

Author Spotlight: Advancing Cell Membrane Biophysics - Exploring Interactions and Challenges Through Experimental and Computational Approaches

Published on: September 1, 2023

Structure-Based Simulation and Sampling of Transcription Factor Protein Movements along DNA from Atomic-Scale Stepping to Coarse-Grained Diffusion

Structure-Based Simulation and Sampling of Transcription Factor Protein Movements along DNA from Atomic-Scale Stepping to Coarse-Grained Diffusion

Published on: March 1, 2022

Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function

Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function

Published on: April 26, 2024

Area of Science:

Computational Biology
Biophysics
Molecular Dynamics

Background:

Implicit solvent force fields offer computational efficiency for molecular dynamics.
However, they often struggle to accurately model disordered proteins.
Existing models may not capture the unique conformational ensembles of these proteins.

Purpose of the Study:

To improve the accuracy of implicit solvent force fields for disordered proteins.
To develop a new force field, GB99dms, by optimizing parameters against explicit solvent simulations.
To demonstrate the utility of differentiable simulations for force field development.

Main Methods:

Jointly optimized 108 parameters of the a99SB-disp force field and GBNeck2 implicit solvent model.
Utilized 5 ns differentiable molecular simulations to train parameters.
Compared simulation results against experimental data and explicit solvent simulations.

Main Results:

The improved force field, GB99dms, better reproduces experimental radius of gyration and secondary structure content for disordered proteins.
GB99dms accurately predicts small molecule binding and improves agreement for amyloid peptide aggregation.
Performance on folded proteins and complexes showed slight degradation.

Conclusions:

Differentiable simulations are effective for training entire force fields to match experimental properties.
GB99dms offers improved modeling of disordered proteins and is available for use in OpenMM.
This approach represents a novel method for developing accurate biomolecular force fields.