{"doi":"10.1038/s42003-022-03411-y","title":"Validated determination of NRG1 Ig-like domain structure by mass spectrometry coupled with computational modeling","abstract":"High resolution hydroxyl radical protein footprinting (HR-HRPF) is a mass spectrometry-based method that measures the solvent exposure of multiple amino acids in a single experiment, offering constraints for experimentally informed computational modeling. HR-HRPF-based modeling has previously been used to accurately model the structure of proteins of known structure, but the technique has never been used to determine the structure of a protein of unknown structure. Here, we present the use of HR-HRPF-based modeling to determine the structure of the Ig-like domain of NRG1, a protein with no close homolog of known structure. Independent determination of the protein structure by both HR-HRPF-based modeling and heteronuclear NMR was carried out, with results compared only after both processes were complete. The HR-HRPF-based model was highly similar to the lowest energy NMR model, with a backbone RMSD of 1.6 Å. To our knowledge, this is the first use of HR-HRPF-based modeling to determine a previously uncharacterized protein structure.","journal":"Communications Biology","year":2022,"id":260917,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":818939,"name":"Alexander Eletsky","orcid":"0000-0002-1291-4315","position":1,"is_corresponding":false},{"id":678473,"name":"Sarah E. Biehn","orcid":"0000-0001-9712-4621","position":2,"is_corresponding":false},{"id":577808,"name":"Charles K. Mobley","orcid":null,"position":3,"is_corresponding":false},{"id":410046,"name":"Monique J. Rogals","orcid":"0000-0003-2796-0549","position":4,"is_corresponding":false},{"id":819398,"name":"Yoonkyoo Kim","orcid":null,"position":5,"is_corresponding":false},{"id":666016,"name":"Sushil K. Mishra","orcid":"0000-0002-3080-9754","position":6,"is_corresponding":false},{"id":364210,"name":"Robert J. Doerksen","orcid":"0000-0002-3789-1842","position":7,"is_corresponding":false},{"id":308314,"name":"Steffen Lindert","orcid":"0000-0002-3976-3473","position":8,"is_corresponding":false},{"id":410048,"name":"James H. Prestegard","orcid":"0000-0002-1602-4790","position":9,"is_corresponding":false},{"id":476783,"name":"Joshua S. Sharp","orcid":"0000-0002-0115-0276","position":10,"is_corresponding":false},{"id":819397,"name":"Niloofar Abolhasani Khaje","orcid":null,"position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T00:26:07.666421Z","pmid":"35551273","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":[]}