Proteins rarely function in isolation as individual monomers. Most biological processes are governed by proteins interacting with other proteins, forming protein complexes whose structures are described in the hierarchy of protein structure as the quaternary representation.

This represents one level of complexity up from tertiary representations, the 3D structure of monomers, which are commonly known since the emergence of AlphaFold2 and the creation of the Protein Data Bank .

Structural information for the vast majority of complexes remains unavailable. While the AlphaFold Protein Structure Database (AFDB), jointly developed by Google DeepMind and EMBL’s European Bioinformatics Institute (EMBL-EBI), transformed access to monomeric protein structures , interaction-aware structural biology at the proteome scale has remained a bottleneck with unique challenges:

Massive combinatorial interaction space

High computational cost for multiple sequence alignment (MSA) generation and protein folding

Inference…