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Protein Networks02:26

Protein Networks

4.1K
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,...
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Ligand Binding Sites02:40

Ligand Binding Sites

13.2K
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...
13.2K
Protein-protein Interfaces02:04

Protein-protein Interfaces

13.3K
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...
13.3K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

9.2K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.2K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

5.9K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.9K
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

5.9K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.9K

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Related Experiment Video

Updated: Sep 13, 2025

Generation of High-Throughput Three-Dimensional Tumor Spheroids for Drug Screening
05:54

Generation of High-Throughput Three-Dimensional Tumor Spheroids for Drug Screening

Published on: September 5, 2018

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Target Mapping in Cancer: Ligandable Protein Pockets on 3D OncoPPI Networks.

Daniela Trisciuzzi1, Orazio Nicolotti1, Gabriele Cruciani2

  • 1Department of Pharmacy, Pharmaceutical Sciences, Università Degli Studi di Bari "Aldo Moro", Via E. Orabona, 4, 70125 Bari, Italy.

Pharmaceuticals (Basel, Switzerland)
|July 30, 2025
PubMed
Summary
This summary is machine-generated.

This study identifies druggable protein pockets in cancer-related protein-protein interactions (PPIs), creating a framework to discover new cancer targets and therapies like PROTACs.

Keywords:
3D oncoPPI networksPPIs modulatorsPROTACsligandable pocketspocketome analysistarget prioritization in cancer

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Area of Science:

  • Structural Biology
  • Computational Biology
  • Cancer Research

Background:

  • Protein-protein interaction (PPI) networks are vital for understanding cancer phenotypes and molecular mechanisms.
  • Targeting protein pockets in cancer-related PPIs (oncoPPIs) offers a strategy to modulate protein function.

Purpose of the Study:

  • To build a comprehensive pocketome of oncoPPIs to identify ligandable pockets.
  • To analyze pocket properties across different cancer types and identify therapeutic targets.
  • To develop a framework for evaluating and prioritizing novel disease targets.

Main Methods:

  • Constructed a pocketome from 314 crystallographically solved oncoPPIs.
  • Employed 3D geometric and energetic descriptors to identify and classify ligandable pockets.
  • Analyzed ligand-bound pockets and built 3D oncoPPI networks to identify protein hubs.

Main Results:

  • Identified key cancer-relevant proteins and interacting residues by integrating network and structural pocket data.
  • Highlighted the therapeutic potential of targeting ligandable 3D oncoPPIs with clinical examples (S100A1, NRP1, CTNNB1, VCP).
  • Created a publicly available reference dataset for future research.

Conclusions:

  • The study provides a flexible framework for evaluating and prioritizing novel disease targets.
  • Targeting ligandable pockets in oncoPPIs presents a promising therapeutic strategy for cancer treatment.
  • The developed dataset and framework will aid future research in cancer drug discovery.