- Structural resolution of protein interactions is crucial for studying mechanisms and disease variants, but many interactions remain unresolved due to limited tools, particularly those involving short linear motifs in disordered protein regions.
- AlphaFold-Multimer shows high sensitivity in predicting domain-motif structures using small protein fragments, but its effectiveness drops with longer fragments or full-length proteins.
- This research introduced a protein fragmentation strategy that successfully predicted new and potentially disease-related protein interfaces in neurodevelopmental disorders, leading to experimental validation of several interactions and highlighting both the promise and limitations of the AlphaFold-Multimer approach.