AlphaPulldown

Information on AlphaPulldown, its application and requirements

What is AlphaPulldown?

AlphaPulldown is a computational pipeline that leverages AlphaFold-Multimer to screen and predict protein-protein interactions (PPIs) systematically. It is especially useful for exploring large-scale interactomes, or validating potential protein partners.

AlphaPulldown automates the process of:

  1. Pairing proteins (from a list or dataset)
  2. Running AlphaFold-Multimer predictions for each pair
  3. Scoring and ranking the results to identify likely binding partners

It's inspired by experimental pulldown assays but done entirely in silico.

Key Features:

  • High-throughput interaction screening
  • Supports pairwise and multi-chain interaction predictions
  • Generates confidence metrics like pLDDT and interface scores (e.g., ipTM)
  • Can be integrated into drug discovery or systems biology workflows

Using AlphaPulldown

Applications

  • Mapping protein interaction networks
  • Identifying binding partners for uncharacterized proteins
  • Validating interactions in silico before experimental testing
  • Structural modeling of protein complexes

Advantages

  • Efficient for large datasets (genome-wide or proteome-wide)
  • Based on AlphaFold-Multimer, offering high structural accuracy
  • Reduces experimental cost and time for interaction discovery

Limitations

  • Accuracy depends on AlphaFold-Multimer’s performance, which may be lower for transient or weak interactions
  • Cannot directly capture dynamic or context-dependent interactions
  • May predict false positives, requiring validation

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