PPI-Miner

PPI-Miner identifies proteins containing sequence or structural motifs similar to a query and models protein–protein interaction complexes to predict binding partners and support applications such as molecular glue discovery and protein vaccine design.

Key Features:

• Motif-matching algorithm: Identifies proteins containing motifs similar to a given query, assessed either sequentially or structurally.
• Binding-mode determination: Determines the binding mode between the motif and its receptor protein.
• Automated PPI complex construction and optimization: Builds and optimizes protein–protein interaction complex models automatically.
• Query types: Uses structural and sequence motifs as primary queries for prediction.
• Proteome-scale screening: Applied to the human proteome to identify candidate substrates, exemplified by 1,739 potential cereblon (CRBN) substrates with 16 experimentally validated predictions reported.
• Automated protocol integration: Integrates automated protocols for PPI complex modeling.
• Scope limitation: Does not include experimental validation components or external database access.

Scientific Applications:

• Rational drug design (molecular glues): Supports rational drug-design efforts including molecular-glue discovery via prediction and modeling of motif-mediated PPIs.
• Protein vaccine design: Applicable to protein vaccine development through motif-based modeling of antigen–receptor interactions.
• Proteome-wide substrate identification: Enables identification of potential substrates across the human proteome, exemplified by CRBN substrate predictions.

Methodology:

The method uses a motif-matching algorithm that (1) identifies proteins with motif similarity to a query using sequence or structural motifs, (2) determines the binding mode between the motif and its receptor protein, and (3) automates construction and optimization of PPI complexes.