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Protein Networks02:26

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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.
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Structural coverage of the human interactome.

Kayra Kosoglu1, Zeynep Aydin1, Nurcan Tuncbag2,3

  • 1Computational Sciences and Engineering, College of Engineering, Koc University, 34450 Istanbul, Turkey.

Briefings in Bioinformatics
|January 5, 2024
PubMed
Summary
This summary is machine-generated.

Structural modeling of protein-protein interactions is crucial for understanding cellular processes. This study reveals limited experimental structural coverage of the human interactome, highlighting the need for computational modeling approaches like AlphaFold.

Keywords:
AlphaFold2PDBhomology modeling databaseshuman interactomehuman proteomeprotein complexesstructural coverage

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Area of Science:

  • Structural Biology
  • Computational Biology
  • Bioinformatics

Background:

  • Cellular functions rely on complex protein-protein interactions within the interactome.
  • Understanding these interactions at a molecular level requires detailed structural information.
  • Assessing the current structural coverage of the human interactome is vital to identify knowledge gaps.

Purpose of the Study:

  • To map experimental protein structures to the human proteome.
  • To evaluate the structural coverage of the human interactome.
  • To explore the potential of computational methods for modeling protein interactions.

Main Methods:

  • Mapping of experimental structures to the human proteome.
  • Integration of homology modeling and deep learning (AlphaFold) for structural enrichment.
  • Collection and curation of human interactome data from literature and databases (HuRI, STRING, HIPPIE).
  • Analysis of structural coverage using experimental and modeled structures, including docking methods.

Main Results:

  • Experimental structures cover only 3.95% of all binary protein-protein interactions in the human interactome.
  • Complementary methods like AlphaFold significantly enrich structural coverage.
  • A substantial portion of interactions from HuRI (12.97%) and filtered STRING/HIPPIE datasets (73.62%/32.94%) show potential for structural modeling.

Conclusions:

  • The human interactome currently has limited experimentally determined structural coverage.
  • Computational modeling, including deep learning, is essential to bridge the gap in structural interactome data.
  • This study provides a comprehensive overview of the structural coverage landscape of the human proteome and interactome.