A simple workflow to identify novel small linear motif (SLiM)-mediated interactions with AlphaFold.

ABSTRACT: Short linear motifs (SLiMs) are highly compact interaction modules embedded within disordered protein regions and are increasingly recognized for their central role in maintaining cellular homeostasis. Due to their small size, degeneracy and transient binding, SLiMs remain difficult to detect both experimentally and computationally. Here, we show that AlphaFold (AF), used via ColabFold, offers a practical and accessible alternative for in-silico screening of new SLiMs targeting a protein of interest. Unlike previous studies that evaluated AlphaFold2 (AF2) using structure-derived benchmarks, we extend this by assessing both AF2 and AF3, using a structure-independent benchmark of 26 interactions absent from PDB homology, and showing that MiniPAE is the most suited AlphaFold metric for SLiM s

SUBMITTER: Veinstein M 

PROVIDER: S-EPMC12476836 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature