OpenAntigens: a structure-aware database for antigen construct design across the human cell-surface and secreted proteome

Abstract

Choosing which region of a protein to express remains poorly standardized in antibody discovery, recombinant reagent generation, structural biology, and computational binder design. For human cell-surface and secreted proteins, this requires reconciling topology, processing, predicted, and experimental structure, modifications, interaction partners, orthologs, paralogs, and cross-reactivity risk before ordering DNA. OpenAntigens is a free, no-login database of construct-design reports for 5328 human secreted, GPI-anchored, single-pass, and multipass proteins. It integrates UniProt topology, AlphaFold pLDDT and PAE, PDB precedent, InterPro and Pfam domains, mouse and cynomolgus orthologs, paralog and family context, Open Targets disease associations, partner and assembly context, and BLAST searches. It provides 55 305 construct suggestions spanning full design regions, PDB-backed boundaries, annotated domains, pLDDT/PAE-derived regions, and membrane-expression options, plus 148 722 sequence-similarity hits to help choose constructs and assess cross-reactivity. For targets with compatible AlphaFold models, the interactive designer links sequence, structure, pLDDT, and PAE, allowing users to revise boundaries and export species-equivalent sequences with real-time cysteine and modification warnings. OpenAntigens places reproducible construct suggestions, comparative context, and browser editing in one workflow, reducing manual reconciliation across resources. OpenAntigens is available at openantigens.org.