One of the main comparisons in the paper is to ClusPro docking of Alphafold-generated monomers. ClusPro uses FFT-based sampling of rotations and translations of

One of the main comparisons in the paper is to ClusPro docking of Alphafold-generated monomers. ClusPro uses FFT-based sampling of rotations and translations of rigid monomers followed by minimization to allow the monomers to relax and adapt. This paper allows significantly more adaptation in the formation of multimers than ClusPro does. Historically, most multimer prediction software has required well structured subunits. And the field was largely built around benchmarks that had structures of subunits [0]. Over the last decade, there has been a increased recognition that many heterodimers are made up of a well structured protein and an intrinsically disordered protein [1] (or intrinsically disordered region of another protein). This lead to a lot of efforts to predict what residues are in the interface and then generating ensembles of "peptide" structures (where peptide is <~15 residues) to model the predicted interface without having to predict larger structure. So, to answer, the structures of the original protein change. An increasingly important area is proteins that don't have much structure as a monomer, but you'll see changes in ones that have well-structured monomers as well. If you dig into some of the difficult cases of the zlab benchmark (using pymol for example), you'll find that in many of those cases, the proteins undergo large conformational changes in forming the complex. [0] https://zlab.umassmed.edu/benchmark/ https://zlab.umassmed.edu/benchmark/ [1] https://en.wikipedia.org/wiki/Intrinsically_disordered_proteins https://en.wikipedia.org/wiki/Intrinsically_disordered_prote...