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AdenoFolds: A Structural Systems Virology Approach to Decode the Adenovirus Interactome

Subject Area Virology
Term since 2026
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 548065690
 
Despite their clinical significance, adenoviruses remain understudied structurally, with most proteins still lacking resolved structures and interaction data. AdenoFolds utilizes recent breakthroughs in AI-driven protein structure prediction to decode the structural architecture and interaction networks of human adenoviruses at the proteome scale. Building on our HerpesFolds database, which mapped the structure and interactome of all nine human herpesviruses, AdenoFolds will deliver a curated structural atlas and interaction network covering all medically relevant adenovirus types. The project uniquely integrates advanced AlphaFold2/3-based in silico predictions with an experimental pipeline that uses a cell-free protein interaction assay and proximity-based proteomics in infected cells. By employing state-of-the-art computational models, we anticipate predicting previously unknown protein folds and interaction sites, facilitating the identification of conserved structural modules and viral-specific adaptations. This hybrid computational-experimental approach will not only chart intra-viral protein complexes but also resolve critical virus-host interaction interfaces, providing mechanistic insights into viral replication, immune modulation, and host specificity. Through close collaboration with consortium partners, we will iteratively refine and validate predictions across systems and functionally dissect adenoviral complexes in their biological context. Dissemination of AdenoFolds via a freely accessible, interactive web platform will ensure broad utility to the research community, supporting hypothesis-driven exploration and ultimately advancing adenovirus biology and therapeutic development.
DFG Programme Research Units
 
 

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