AlphaFold2 enables accurate deorphanization of ligands to single-pass receptors.

ABSTRACT: Secreted proteins play crucial roles in paracrine and endocrine signaling; however, identifying ligand-receptor interactions remains challenging. Here, we benchmarked AlphaFold2 (AF2) as a screening approach to identify extracellular ligands to single-pass transmembrane receptors. Key to the approach is the optimization of AF2 input and output for screening ligands against receptors to predict the most probable ligand-receptor interactions. The predictions were performed on ligand-receptor pairs not used for AF2 training. We demonstrate high discriminatory power and a success rate of close to 90% for known ligand-receptor pairs and 50% for a diverse set of experimentally validated interactions. Further, we show that screen accuracy does not correlate linearly with prediction of ligand-rece

SUBMITTER: Banhos Danneskiold-Samsoe N 

PROVIDER: S-EPMC12147870 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature