Unveiling Interaction Signatures Across Viral Pathogens through VASCO: Viral Antigen-Antibody Structural COmplex...

Area of Science:

• Structural biology
• Immunology
• Computational biology

Background:

• Viral antigen-antibody (Ag-Ab) interactions are vital for immune responses, pathogen neutralization, and vaccine development.
• Understanding the structural basis of these interactions is essential for predicting immune recognition and designing effective therapeutics.
• A scarcity of curated structural benchmarks for viral Ag-Ab interactions hinders progress.

Purpose of the Study:

• To present VASCO (Viral Antibody-antigen Structural COmplex dataset), a comprehensive, high-resolution structural resource for viral Ag-Ab complexes.
• To identify distinct sequence and structural features differentiating viral Ag-Ab binding from general protein-protein interactions.
• To provide a foundation for improved computational modeling and immunogen design.

Main Methods:

• Compiled ~1225 viral Ag-Ab complexes from the Protein Data Bank (PDB).
• Refined complex structures using energy minimization.
• Compared structural and sequence features of viral Ag-Ab complexes against general protein-protein interactions (GPPI).

Main Results:

• VASCO offers a non-redundant, high-resolution structural reference for diverse viral Ag-Ab complexes (e.g., Coronaviruses, Influenza, HIV).
• Distinct sequence-space interactions, secondary structure preferences, and latent features characterize viral Ag-Ab binding compared to GPPI.
• General predictive models trained on GPPI show limitations for viral Ag-Ab interactions.

Conclusions:

• VASCO is a critical resource for advancing viral immunology and improving predictive modeling.
• The dataset facilitates the design of immunogens to elicit protective antibody responses.
• VASCO supports enhanced docking, affinity prediction, and antiviral therapeutic development for pandemic preparedness.