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

ABSTRACT: Secreted proteins play crucial roles in paracrine and endocrine signaling; however, identifying novel ligand-receptor interactions remains challenging. Here, we benchmarked AlphaFold as a screening approach to identify extracellular ligand-binding pairs using a structural library of single-pass transmembrane receptors. Key to the approach is the optimization of AlphaFold input and output for screening ligands against receptors to predict the most probable ligand-receptor interactions. Importantly, the predictions were performed on ligand-receptor pairs not used for AlphaFold 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. These results demonstrate proo

SUBMITTER: Danneskiold-Samsoe NB 

PROVIDER: S-EPMC10055078 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature