AlphaFold Database expands to proteome-scale quaternary structures

Han, Y.; Tsenkov, M. I.; Venanzi, N. A. E.; Bertoni, D.; Cha, S.; Chacon, A.; Dietrich, N.; Fomitchev, B.; Goldtzvik, Y.; Hsu, D.; Austin, J.; Ellaway, J.; Didi, K.; Kovalevskiy, O.; Lasecki, D.; Laydon, A.; Livne, M.; Magana, P.; Majewski, M.; Nair, S.; Paramval, U.; Patel, N.; Patel, R.; Pidruchna, I.; Santini Lopez, B.; Sohani, P.; Tanweer, A.; Tran, D.; Tretina, K.; Vollmar, M.; Vu, Q.; Zidek, A.; Velankar, S.; Steinegger, M.; Fleming, J.; Mirdita, M.; Dallago, C.

doi:10.64898/2026.03.27.714458

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bioRxiv · 10.64898/2026.03.27.714458

AlphaFold Database expands to proteome-scale quaternary structures

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Abstract

Protein function is governed by molecular interactions, yet structural coverage of these interactions remains sparse. The AlphaFold Protein Structure Database (AFDB) transformed access to accurate monomeric protein structures at scale. Here, we expand the AFDB to quaternary structures by predicting 31M candidate homo- and heterodimeric protein complexes, compiled from 4,777 proteomes, including model- and global health organisms. We established confidence criteria via analysis of experimentally determined structures, resulting in 1.81M high-confidence predictions. These models enabled the discovery of emergent structures and topologies not present in monomeric predictions. Additionally, the top 1% of structural clusters accounted for [~]44% of all complexes, and [~]8.3% of clusters were conserved across multiple domains of life, pointing to a substantial fraction of ancient, universally retained assemblies. Structural search highlighted that high-confidence predictions are anchored in experimental multimer space, yet 31.3% extend beyond detectable PDB coverage. These freely accessible proteome-scale predictions facilitate functional and mechanistic hypothesis generation across biology.

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Han, Y., Tsenkov, M. I., Venanzi, N. A. E., Bertoni, D., Cha, S., Chacon, A., Dietrich, N., Fomitchev, B., Goldtzvik, Y., Hsu, D., Austin, J., Ellaway, J., Didi, K., Kovalevskiy, O., Lasecki, D., Laydon, A., Livne, M., Magana, P., Majewski, M., Nair, S., Paramval, U., Patel, N., Patel, R., Pidruchna, I., Santini Lopez, B., Sohani, P., Tanweer, A., Tran, D., Tretina, K., Vollmar, M., Vu, Q., Zidek, A., Velankar, S., Steinegger, M., Fleming, J., Mirdita, M., Dallago, C.. 2026-03-29. AlphaFold Database expands to proteome-scale quaternary structures. https://doi.org/10.64898/2026.03.27.714458

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