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Related Concept Videos

Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
The Proteasome02:18

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Tagging and Fusion Proteins01:24

Tagging and Fusion Proteins

Proteins are involved in several cellular processes and biochemical reactions. Analyzing a specific protein of interest requires it to be isolated from the other proteins in the cell. This is achieved by overexpressing the specific gene in a suitable host to produce large quantities of the target protein. A tag or label is recombined with the gene to produce a fusion protein containing the target protein and the tag. The tags on these fusion proteins can then be used for easy detection and...

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Related Experiment Video

Updated: Jul 17, 2026

In Vitro Analysis of E3 Ubiquitin Ligase Function
06:06

In Vitro Analysis of E3 Ubiquitin Ligase Function

Published on: May 14, 2021

COMPASS: A Computational Pipeline to Identify Linkers Predicting Ubiquitinable PROTAC-Induced Ternary Complexes.

Sébastien Sueron1,2,3, Sayyed Jalil Mahdizadeh4, Eric Chevet2,5

  • 1ISCR-UMR CNRS 6226, Faculty of Pharmacy, University of Rennes, Rennes, France.

Chemmedchem
|July 15, 2026
PubMed
Summary

PROteolysis Targeting Chimeras (PROTACs) are novel therapeutics for targeted protein degradation. A new computational tool, COMPASS, screens PROTAC linkers to predict successful ternary complex formation and degradation, improving rational drug design.

Keywords:
PROTACdegradationmedicinal chemistrymolecular modelingternary complexubiquitination

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Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations
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Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations

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Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model

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Related Experiment Videos

Last Updated: Jul 17, 2026

In Vitro Analysis of E3 Ubiquitin Ligase Function
06:06

In Vitro Analysis of E3 Ubiquitin Ligase Function

Published on: May 14, 2021

Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations
10:26

Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations

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Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model
09:00

Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model

Published on: April 17, 2026

Area of Science:

  • Biochemistry
  • Computational Biology
  • Drug Discovery

Background:

  • PROteolysis TArgeting Chimeras (PROTACs) are bifunctional molecules that induce targeted protein degradation.
  • Rational PROTAC design is challenging due to complex ternary structures and linker roles.

Purpose of the Study:

  • Introduce COMPASS, a computational pipeline for screening PROTAC linker libraries.
  • Assess ternary complex formation and ubiquitination potential for PROTAC design.

Main Methods:

  • COMPASS uses structure-based screening to evaluate linker libraries.
  • It functions as a negative filter to eliminate non-productive linkers.
  • Benchmarking involved 20 crystallographic structures and retrospective validation on 112 PROTACs across 8 systems.

Main Results:

  • COMPASS achieved <6 Å Cα-RMSD across 20 crystallographic structures.
  • Retrospective validation showed 93% recall for degradation endpoints.
  • The method excels in linker-geometry-limited scenarios.

Conclusions:

  • COMPASS enhances PROTAC design by computationally screening linkers.
  • It effectively predicts ternary complex formation and degradation potential.
  • This tool complements existing methods by addressing linker geometry limitations.