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Related Concept Videos

Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

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...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

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...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

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...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

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 pathway,...
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

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 the...
Allosteric Regulation01:08

Allosteric Regulation

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...

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Related Experiment Video

Updated: Jul 12, 2026

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions
06:50

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions

Published on: January 26, 2024

Multiply Perturbed Response: A Computational Protocol to Identify Cooperative Allosteric Residue Combinations Driving

Kübranur Kazan1, Melike Berksoz1, Burak Kocuk1

  • 1Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey.

Bio-Protocol
|July 10, 2026
PubMed
Summary

Multiply Perturbed Response (MPR) identifies key allosteric residue combinations driving protein conformational changes. This method enhances previous techniques by simulating simultaneous multi-residue perturbations for deeper mechanistic insights.

Keywords:
Allosteric residue combinationsConformational transitionElastic network modelLinear response theoryMultiply perturbed responseOverlap maximizationVariance-covariance matrix

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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

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15N CPMG Relaxation Dispersion for the Investigation of Protein Conformational Dynamics on the µs-ms Timescale
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15N CPMG Relaxation Dispersion for the Investigation of Protein Conformational Dynamics on the µs-ms Timescale

Published on: April 19, 2021

Related Experiment Videos

Last Updated: Jul 12, 2026

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions
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Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions

Published on: January 26, 2024

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
07:08

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Published on: July 14, 2015

15N CPMG Relaxation Dispersion for the Investigation of Protein Conformational Dynamics on the µs-ms Timescale
08:09

15N CPMG Relaxation Dispersion for the Investigation of Protein Conformational Dynamics on the µs-ms Timescale

Published on: April 19, 2021

Area of Science:

  • Computational Biology
  • Structural Biology
  • Biophysics

Background:

  • Protein function relies on dynamic conformational changes.
  • Understanding allosteric mechanisms is crucial for protein function insights.
  • Molecular dynamics (MD) simulations capture protein dynamics but struggle with rare events.

Purpose of the Study:

  • Introduce Multiply Perturbed Response (MPR) to overcome limitations of single-residue perturbation methods.
  • Enable identification of allosteric residue combinations driving conformational transitions.
  • Provide a versatile framework for both structure-based and trajectory-based analyses.

Main Methods:

  • MPR extends Perturbation Response Scanning (PRS) by applying simultaneous perturbations to multiple residues.
  • Utilizes elastic network models and linear response theory.
  • Workflow includes structure preparation, displacement, covariance calculations, overlap analysis, and visualization.

Main Results:

  • Identifies combinations of residues that maximize overlap (Omax), indicating cooperative allosteric effects.
  • Generates ranked residue combinations, force vectors, and visualization files.
  • MPR captures conformational transitions from combined residue effects, unlike single-residue methods.

Conclusions:

  • MPR offers a robust, reproducible, and accessible method for identifying allosteric hotspots.
  • Facilitates mechanistic interpretation and experimental validation of protein allostery.
  • Enhances the study of protein dynamics and allosteric regulation through multi-residue perturbation analysis.