Summary
ipTM can change when irrelevant domains or disordered residues are trimmed even if the predicted binding interface is unchanged (1). The direction depends on construct composition: extra residues can increase ipTM when one partner is a compact domain, but can substantially decrease it when both chains contain disorder or accessory domains. This follows from scoring whole chains and using a length-dependent , rather than from a change in the interface itself. ipSAE mitigates the dependence by restricting the score to residue pairs with good interchain PAE.
See also
- Antigen size biases AlphaFold3 antibody-antigen confidence
- Protein structure prediction and design confidence metrics do not correlate with binding affinity
1.
Dunbrack RL. Res ipSAE loquuntur: What’s wrong with AlphaFold’s ipTM score and how to fix. openRxiv; 2025. Available from: https://doi.org/10.1101/2025.02.10.637595