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Related Concept Videos

Protein-protein Interfaces02:04

Protein-protein Interfaces

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 polypeptide...
Protein-Protein Interfaces02:04

Protein-Protein Interfaces

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 polypeptide...
Protein Networks02:26

Protein Networks

An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
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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Updated: May 14, 2026

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
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Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Published on: December 1, 2020

Using a fragment-based approach to target protein-protein interactions.

Duncan E Scott1, Matthias T Ehebauer, Tara Pukala

  • 1Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.

Chembiochem : a European Journal of Chemical Biology
|January 25, 2013
PubMed
Summary

This study introduces a fragment-based drug discovery approach targeting the BRCA2-RAD51 interaction, crucial for DNA repair. Researchers identified novel small molecules binding to this protein-protein interface, offering new therapeutic avenues.

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Last Updated: May 14, 2026

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
08:31

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Published on: December 1, 2020

Genome-wide Protein-protein Interaction Screening by Protein-fragment Complementation Assay (PCA) in Living Cells
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Published on: March 3, 2015

Covalent Fragment Screening Using the Quantitative Irreversible Tethering Assay
06:17

Covalent Fragment Screening Using the Quantitative Irreversible Tethering Assay

Published on: February 28, 2025

Area of Science:

  • Drug Discovery
  • Chemical Biology
  • Structural Biology

Background:

  • Protein-protein interactions (PPIs) are challenging drug targets.
  • Fragment-based drug discovery (FBDD) is an emerging methodology.
  • Targeting the BRCA2-RAD51 interaction is key for cancer therapy.

Purpose of the Study:

  • To develop a fragment-based approach for targeting the BRCA2-RAD51 interaction.
  • To identify small molecules that inhibit this critical protein-protein interaction.
  • To establish a screening pipeline applicable to similar targets.

Main Methods:

  • Protein engineering of a monomeric RAD51 orthologue.
  • Fragment screening using biophysical techniques.
  • Validation via isothermal titration calorimetry (ITC), NMR, and X-ray crystallography.

Main Results:

  • Identified fragment hits binding to a shallow pocket on RAD51.
  • The binding site mimics the interaction with BRCA2's FxxA motif.
  • First report of small molecules binding to this specific PPI site.

Conclusions:

  • Demonstrated the feasibility of FBDD for the BRCA2-RAD51 interaction.
  • Provides novel chemical starting points for developing inhibitors.
  • The methodology is potentially applicable to other challenging PPI targets.