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Related Concept Videos

Conserved Binding Sites01:49

Conserved Binding Sites

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 analyses the...
Conserved Binding Sites01:49

Conserved Binding Sites

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 analyses the...
The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
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...
Ligand Binding Sites02:40

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Ligand Binding Sites02:40

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...

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Related Experiment Video

Updated: May 14, 2026

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
11:34

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins

Published on: August 9, 2019

Computational methods for controlling binding specificity.

Oz Sharabi1, Ariel Erijman, Julia M Shifman

  • 1Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.

Methods in Enzymology
|February 21, 2013
PubMed
Summary
This summary is machine-generated.

Computational protein design offers a fast and cost-effective method to control protein-binding specificity. This approach enhances interactions with desired targets while minimizing unwanted binding, enabling precise protein engineering for research and drug development.

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

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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

Related Experiment Videos

Last Updated: May 14, 2026

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
11:34

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins

Published on: August 9, 2019

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

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

Area of Science:

  • Biochemistry
  • Computational Biology
  • Protein Engineering

Background:

  • Controlling protein-binding specificity is crucial for understanding biological signaling networks and for successful drug design.
  • Nonspecific protein binding is a significant cause of drug candidate failure in pharmaceutical development.
  • Engineering proteins with tailored binding specificities is essential for advancing both fundamental biological research and applied therapeutic strategies.

Purpose of the Study:

  • To develop a computational approach for precisely controlling protein-binding specificity.
  • To engineer proteins that exhibit enhanced interactions with specific targets and reduced interactions with off-targets.
  • To design multispecific proteins capable of simultaneous interaction with multiple predefined protein targets.

Main Methods:

  • Utilized computational protein design to optimize amino acid sequences for desired binding interactions.
  • Developed algorithms to enhance specificity by favoring interactions with one target while disfavoring interactions with others.
  • Explored the design of multispecific proteins through computational sequence optimization.

Main Results:

  • Demonstrated the ability to computationally enhance the binding specificity of proteins.
  • Showcased the design of proteins with improved target interaction profiles.
  • Successfully designed multispecific proteins for simultaneous interaction with multiple targets.
  • The computational method proved to be fast, low-cost, and capable of considering numerous binding partners.

Conclusions:

  • Computational protein design provides an effective alternative to experimental display technologies for manipulating binding specificity.
  • This approach offers a rapid, economical, and scalable solution for engineering protein interactions.
  • The developed methods hold significant potential for applications in fundamental biology, drug discovery, and the development of novel therapeutics.