{"entity": "publication", "iuid": "6b000114117d463389b8268aa09d576f", "timestamp": "2026-08-20T20:37:08.611Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6b000114117d463389b8268aa09d576f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6b000114117d463389b8268aa09d576f"}}, "title": "AI-first structural identification of pathogenic protein target interfaces.", "authors": [{"family": "Saluri", "given": "Mihkel", "initials": "M"}, {"family": "Landreh", "given": "Michael", "initials": "M"}, {"family": "Bryant", "given": "Patrick", "initials": "P", "orcid": "0000-0003-3439-1866", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6a683bcf98234ff09b2398976583b66f.json"}}], "type": "journal article", "published": "2025-06-00", "journal": {"title": "PLoS Comput Biol", "issn": "1553-7358", "volume": "21", "issue": "6", "pages": "e1013168", "issn-l": "1553-734X"}, "abstract": "The risk of pandemics is increasing as global population growth and interconnectedness accelerate. Understanding the structural basis of protein-protein interactions between pathogens and hosts is critical for elucidating pathogenic mechanisms and guiding treatment or vaccine development. Despite 21,064 experimentally supported human-pathogen interactions in the HPIDB, only 52 have resolved structures in the PDB, representing just 0.2%. Advances in protein complex structure prediction, such as AlphaFold, now enable highly accurate modelling of heterodimeric complexes, though their application to host-pathogen interactions, which have distinct evolutionary dynamics, remains underexplored. Here, we investigate the structural protein-protein interaction network between humans and ten pathogens, predicting structures for 9,452 interactions, only 10 of which have known structures. We identify 30 interactions with an expected TM-score \u22650.9, tripling the structural coverage in these networks. A detailed analysis of the Francisella tularensis dihydroprolyl dehydrogenase (IPD) complex with human immunoglobulin kappa constant (IGKC) using homology modelling and native mass spectrometry confirms a predicted 1:2:1 heterotetramer, suggesting potential roles in immune evasion. These findings highlight the transformative potential of structure prediction for rapidly advancing vaccine and drug development against novel pathogenic targets.", "doi": "10.1371/journal.pcbi.1013168", "pmid": "40570050", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12225977"}, {"db": "pii", "key": "PCOMPBIOL-D-25-00468"}], "notes": [], "created": "2026-08-20T12:43:19.933Z", "modified": "2026-08-20T12:43:20.006Z"}