AlphaFold Ensemble Competition Screens Enable Peptide Binder Design with Single-Residue Sensitivity.

ABSTRACT: Understanding the relationship between the sequence and binding energy in peptide-protein interactions is an important challenge in chemical biology. A prominent example is ubiquitin interacting motifs (UIMs), which are short peptide sequences that recognize ubiquitin and which bind individual ubiquitin proteins with a weak affinity. Though the sequence characteristics of UIMs are well understood, the relationship between the sequence and ubiquitin binding affinity has not yet been fully characterized. Herein, we study the first UIM of Vps27 as a model system. Using an experimental alanine scan, we were able to rank the relative contribution of each hydrophobic residue of this UIM to ubiquitin binding. These results were correlated with AlphaFold displacement studies, in which AlphaFold is

SUBMITTER: Vosbein P 

PROVIDER: S-EPMC11494501 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature