Systematic discovery of protein interaction interfaces using AlphaFold and experimental validation.

ABSTRACT: Structural resolution of protein interactions enables mechanistic and functional studies as well as interpretation of disease variants. However, structural data is still missing for most protein interactions because we lack computational and experimental tools at scale. This is particularly true for interactions mediated by short linear motifs occurring in disordered regions of proteins. We find that AlphaFold-Multimer predicts with high sensitivity but limited specificity structures of domain-motif interactions when using small protein fragments as input. Sensitivity decreased substantially when using long protein fragments or full length proteins. We delineated a protein fragmentation strategy particularly suited for the prediction of domain-motif interfaces and applied it to interaction

SUBMITTER: Lee CY 

PROVIDER: S-EPMC10883280 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature