Systematic exploration of predicted quaternary structures within pandemic-relevant viral proteomes
Han, Y.; Narain, R.; Abbara, R.; Afonso, M. Q. L.; Austin, J.; Bertoni, D.; Cha, S.; Cowen-Rivers, A. I.; Ellaway, J. I. J.; Fransos, D.; Gion, K.; Hsu, D.; Hulo, C.; Kim, R. S.; Kovalevskiy, O.; Laydon, A.; Mason, J.; Nair, S.; Paramval, U.; Patel, N.; Patel, R.; Pidruchna, I.; Ratcliff, J.; Tsenkov, M. I.; Vanenzi, N. A. E.; Vollmar, M.; Wahome, N.; Wong, E. L. H.; Fleming, J. R.; Velankar, S.; Mirdita, M.; Le Mercier, P.; Steinegger, M.; Dallago, C.; Grove, J.
Show abstract
Mechanistic understanding of viral protein-protein interactions enables global health security and pandemic preparedness, yet experimental characterisation remains difficult, costly, and often restricted to specialised laboratories. Here, we describe an in silico campaign using AlphaFold2 and AlphaFold-Multimer to predict monomers and dimer structures within 2,812 viral proteomes from 23 viral families relevant to human health. We report high-confidence predicted structures of 5,279 hetero-, and 2,749 homo-dimers. Structural clustering of interfaces reduces the set fivefold to 1,598 consolidated by form and function, of which 471 (29.5%) lacked detectable similarity to experimentally determined interfaces in the PDB. These clusters yielded two notable findings: new data on vaccinology-relevant glycoproteins, and accurate prediction of the specificity and cleavage-site recognition of viral proteases, which are targets for anti-viral development. Viral monomers and high-confidence dimers are available for interactive browsing in the Pandemic Preparedness Portal of the AlphaFold Database (https://alphafold.ebi.ac.uk/), and the full dataset is available for bulk download.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Structural characterization of the oligomerization of full-length Hantaan virus polymerase into symmetric dimers and hexamers 95%
- Cryo-EM structure of coronavirus-HKU1 haemagglutinin esterase reveals architectural changes arising from prolonged circulation in humans 94%
- Structural landscape of the Respiratory Syncytial Virus nucleocapsids 94%
Similar papers in this journal
- High diversity in Delta variant across countries revealed via genome-wide analysis of SARS-CoV-2 beyond the Spike protein 93%
- AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor 91%
- Human phospho-signaling networks of SARS-CoV-2 infection are rewired by population genetic variants 91%
Similar papers in this journal
- Structural Studies of Nedicistrovirus IRES-Driven, Initiation Factor-independent Translation Shed Light on Key Steps of Eukaryotic Translation Elongation 94%
- Structural basis of multitasking by the apicoplast DNA polymerase from Plasmodium falciparum 93%
- Oncodrive3D: Fast and accurate detection of structural clusters of somatic mutations under positive selection 92%
Similar papers in this journal
"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.