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FlyPredictome: A structural atlas of predicted protein-protein interactions in Drosophila

Kim, A.-R.; Comjean, A.; Veal, A.; Rodiger, J.; Han, M.; Hu, Y.; Perrimon, N.

2026-05-11 bioinformatics
10.64898/2026.04.14.718529 bioRxiv
Show abstract

Protein-protein interactions (PPIs) are fundamental to cellular function. Yet most Drosophila PPIs remain structurally uncharacterized despite the wealth of genetic and biochemical data available for this organism. Here we present FlyPredictome, a structural interactome based on 1.5 million pairwise AlphaFold-Multimer predictions. Using a local confidence metric that performs robustly for interactions involving flexible and disordered proteins, we systematically assess experimentally reported Drosophila PPIs and predict direct binding interfaces at residue-level resolution. Testing their functional relevance, we find that phenotype-associated missense mutations are enriched at predicted interaction interfaces. Building on these validated predictions, we construct an evidence-supported PPI network, revealing modular organization from signaling pathways to individual pro-tein complexes. FlyPredictome is available as an open database, providing a structural foundation for interaction discovery in Drosophila.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.