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

Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

7.9K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
7.9K
Allosteric Regulation01:08

Allosteric Regulation

58.3K
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
58.3K
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

5.8K
Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.8K
The Two-State Receptor Model01:29

The Two-State Receptor Model

2.0K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
2.0K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

4.8K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
4.8K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

8.5K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.5K

You might also read

Related Articles

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

Sort by
Same author

From discovery to the clinic: structural insights, engineering options, clinical, and 'next wave' applications of camelid-derived single-domain antibodies.

mAbs·2025
Same author

Toward the Design of Allosteric Effectors: Gaining Comprehensive Control of Drug Properties and Actions.

Journal of medicinal chemistry·2024
Same author

Molecular Modeling of the Deamidation Reaction in Solution: A Theoretical-Computational Study.

The journal of physical chemistry. B·2023
Same author

AlloMAPS 2: allosteric fingerprints of the AlphaFold and Pfam-trRosetta predicted structures for engineering and design.

Nucleic acids research·2022
Same author

Exploring the Allosteric Territory of Protein Function.

The journal of physical chemistry. B·2021
Same author

Exploring chromatin hierarchical organization via Markov State Modelling.

PLoS computational biology·2019
Same journal

Anharmonic phonons via quantum thermal bath simulations.

The Journal of chemical physics·2026
Same journal

Quantum simulation of alignment dependent differential cross sections in co-propagating molecular beams at cold collision energies.

The Journal of chemical physics·2026
Same journal

Non-additive ion effects on the coil-globule equilibrium of a generic polymer in aqueous salt solutions.

The Journal of chemical physics·2026
Same journal

Insights into the unexpected small reduction of the temperature of maximum density of water by lithium chloride addition.

The Journal of chemical physics·2026
Same journal

Optical frequency comb double-resonance spectroscopy of the 9030-9175 cm-1 states of ethylene.

The Journal of chemical physics·2026
Same journal

Time reversal breaking of colloidal particles in cells.

The Journal of chemical physics·2026
See all related articles

Related Experiment Video

Updated: Aug 3, 2025

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
08:00

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

Published on: October 4, 2024

647

Sequence-dependent model of allosteric communication.

Enrico Guarnera1, Igor N Berezovsky1

  • 1Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), 30 Biopolis Street, #07-01, Matrix, Singapore 138671.

The Journal of Chemical Physics
|April 8, 2023
PubMed
Summary
This summary is machine-generated.

A new computational model integrates protein sequence into allosteric communication analysis. This approach reveals that the interplay between allosteric site energy and overall structural dynamics governs allosteric modulation.

More Related Videos

Structure-Based Simulation and Sampling of Transcription Factor Protein Movements along DNA from Atomic-Scale Stepping to Coarse-Grained Diffusion
09:17

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

3.2K
Author Spotlight: Evaluation of Protein-Condensate Dynamics in Live Human Cells
06:48

Author Spotlight: Evaluation of Protein-Condensate Dynamics in Live Human Cells

Published on: January 5, 2024

3.8K

Related Experiment Videos

Last Updated: Aug 3, 2025

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
08:00

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

Published on: October 4, 2024

647
Structure-Based Simulation and Sampling of Transcription Factor Protein Movements along DNA from Atomic-Scale Stepping to Coarse-Grained Diffusion
09:17

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

3.2K
Author Spotlight: Evaluation of Protein-Condensate Dynamics in Live Human Cells
06:48

Author Spotlight: Evaluation of Protein-Condensate Dynamics in Live Human Cells

Published on: January 5, 2024

3.8K

Area of Science:

  • Computational Biology
  • Protein Dynamics
  • Biophysics

Background:

  • Allosteric regulation is crucial in proteins and protein complexes, driving the need for advanced computational models.
  • Understanding the influence of amino acid sequence on allosteric communication is a key challenge in protein engineering.
  • Current models often lack the sequence-specific details necessary for precise allosteric analysis and drug design.

Purpose of the Study:

  • To develop a novel network-based computational model for analyzing allosteric communication.
  • To incorporate sequence dependence into allosteric modeling by combining structural and residue-level potentials.
  • To identify key determinants of allosteric modulation in proteins.

Main Methods:

  • Developed a network-based model combining a structure-based statistical mechanical model of allostery.
  • Integrated the Miyazawa-Jernigan residue-residue potential to account for sequence dependence.
  • Applied the model to analyze allosteric communication in five well-characterized allosteric proteins.

Main Results:

  • The model successfully incorporates sequence information into the analysis of allosteric communication.
  • Identified two critical determinants of allosteric modulation: free energy from the allosteric site and background structural dynamics.
  • Demonstrated that the combined effect of these determinants dictates the extent of allosteric modulation.

Conclusions:

  • The developed model provides a more comprehensive understanding of allostery by including sequence effects.
  • Allosteric modulation is governed by the interplay between specific site-to-site energy transfer and global protein dynamics.
  • Future studies should explore the dependence of these determinants on protein structure, oligomerization, and sequence variation.