{"doi":"10.1101/2023.03.16.531341","title":"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 proof-of-concept of a rapid and accurate screening platform to predict high-confidence cell-surface receptors for a diverse set of ligands by structural binding prediction, with potentially wide applicability for the understanding of cell-cell communication.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":389869,"datarank":0.4335557636844247,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.0,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1161071,"name":"Deniz Kavi","orcid":null,"position":1,"is_corresponding":false},{"id":260360,"name":"Kevin M. Jude","orcid":"0000-0002-3675-5136","position":2,"is_corresponding":false},{"id":920871,"name":"Silas Boye Nissen","orcid":"0000-0002-9473-4755","position":3,"is_corresponding":false},{"id":258263,"name":"Lianna W. Wat","orcid":"0000-0001-6998-0594","position":4,"is_corresponding":false},{"id":920870,"name":"Laetitia Coassolo","orcid":"0000-0003-2138-4819","position":5,"is_corresponding":false},{"id":348821,"name":"Meng Zhao","orcid":"0000-0002-5415-8335","position":6,"is_corresponding":false},{"id":1161072,"name":"Galia Asae Santana-Oikawa","orcid":null,"position":7,"is_corresponding":false},{"id":1161073,"name":"Beatrice Blythe Broido","orcid":null,"position":8,"is_corresponding":false},{"id":218189,"name":"K. Christopher García","orcid":"0000-0001-9273-0278","position":9,"is_corresponding":false},{"id":348824,"name":"Katrin J. Svensson","orcid":"0000-0001-5376-5128","position":10,"is_corresponding":false},{"id":926864,"name":"Niels Banhos Danneskiold‐Samsøe","orcid":"0000-0002-2889-5630","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:18:27.054415Z","pmid":"36993313","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}