Accurate affinity models for SH2 domains from peptide binding assays and free-energy regression.

ABSTRACT: Short linear peptide motifs play important roles in phosphotyrosine-dependent signaling networks. They can act both as substrates of kinases and phosphatases and as ligands of peptide binding domains. SH2 domains bind specifically to tyrosine-phosphorylated proteins, with the affinity of the interaction depending strongly on the flanking sequence. In recent years, protein display technologies and next-generation sequencing (NGS) have allowed researchers to profile SH2 domain binding across large libraries of candidate ligands. Here, we present a concerted experimental and computational strategy that updates such specificity profiling from classification to quantification. Multi-round affinity selection on random phosphopeptide libraries yields NGS data suitable for training an additive mod

SUBMITTER: Gagoski D 

PROVIDER: S-EPMC12521615 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature