{"doi":"10.1002/ange.201511711","title":"Rapid Determination of Fast Protein Dynamics from NMR Chemical Exchange Saturation Transfer Data","abstract":"<jats:title>Abstract</jats:title><jats:p>Functional motions of <jats:sup>15</jats:sup>N‐labeled proteins can be monitored by solution NMR spin relaxation experiments over a broad range of timescales. These experiments however typically take of the order of several days to a week per protein. Recently, NMR chemical exchange saturation transfer (CEST) experiments have emerged to probe slow millisecond motions complementing <jats:italic>R</jats:italic><jats:sub>1<jats:italic>ρ</jats:italic></jats:sub> and CPMG‐type experiments. CEST also simultaneously reports on site‐specific <jats:italic>R</jats:italic><jats:sub>1</jats:sub> and <jats:italic>R</jats:italic><jats:sub>2</jats:sub> parameters. It is shown here how CEST‐derived <jats:italic>R</jats:italic><jats:sub>1</jats:sub> and <jats:italic>R</jats:italic><jats:sub>2</jats:sub> relaxation parameters can be measured within a few hours at an accuracy comparable to traditional relaxation experiments. Using a “lean” version of the model‐free approach <jats:italic>S</jats:italic><jats:sup>2</jats:sup> order parameters can be determined that match those from the standard model‐free approach applied to <jats:sup>15</jats:sup>N <jats:italic>R</jats:italic><jats:sub>1</jats:sub>, <jats:italic>R</jats:italic><jats:sub>2</jats:sub>, and {<jats:sup>1</jats:sup>H}‐<jats:sup>15</jats:sup>N NOE data. The new methodology, which is demonstrated for ubiquitin and arginine kinase (42 kDa), should serve as an effective screening tool of protein dynamics from picosecond‐to‐millisecond timescales.</jats:p>","journal":"Angewandte Chemie","year":2016,"id":658522,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":669060,"name":"Alexandar L. Hansen","orcid":"0000-0003-4474-7141","position":1,"is_corresponding":false},{"id":692014,"name":"Yu Peng","orcid":"0000-0001-9116-1739","position":2,"is_corresponding":false},{"id":669065,"name":"Rafael Brüschweiler","orcid":"0000-0003-3649-4543","position":3,"is_corresponding":false},{"id":1719072,"name":"Yina Gu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Rapid Determination of Fast Protein Dynamics from NMR Chemical Exchange Saturation Transfer Data","abstract":"<jats:title>Abstract</jats:title><jats:p>Functional motions of <jats:sup>15</jats:sup>N‐labeled proteins can be monitored by solution NMR spin relaxation experiments over a broad range of timescales. These experiments however typically take of the order of several days to a week per protein. Recently, NMR chemical exchange saturation transfer (CEST) experiments have emerged to probe slow millisecond motions complementing <jats:italic>R</jats:italic><jats:sub>1<jats:italic>ρ</jats:italic></jats:sub> and CPMG‐type experiments. CEST also simultaneously reports on site‐specific <jats:italic>R</jats:italic><jats:sub>1</jats:sub> and <jats:italic>R</jats:italic><jats:sub>2</jats:sub> parameters. It is shown here how CEST‐derived <jats:italic>R</jats:italic><jats:sub>1</jats:sub> and <jats:italic>R</jats:italic><jats:sub>2</jats:sub> relaxation parameters can be measured within a few hours at an accuracy comparable to traditional relaxation experiments. Using a “lean” version of the model‐free approach <jats:italic>S</jats:italic><jats:sup>2</jats:sup> order parameters can be determined that match those from the standard model‐free approach applied to <jats:sup>15</jats:sup>N <jats:italic>R</jats:italic><jats:sub>1</jats:sub>, <jats:italic>R</jats:italic><jats:sub>2</jats:sub>, and {<jats:sup>1</jats:sup>H}‐<jats:sup>15</jats:sup>N NOE data. The new methodology, which is demonstrated for ubiquitin and arginine kinase (42 kDa), should serve as an effective screening tool of protein dynamics from picosecond‐to‐millisecond timescales.</jats:p>","is_dataset_classified":null,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19965766","pmcid":null,"openalex_id":"https://openalex.org/W4242401646","authors":[],"funders":[{"funder_name":"National Science Foundation","grant_id":"MCB-1360966","title":null}],"total_grants":1,"fwci":0.4332,"citation_percentile":0.84977802,"influential_citations":0,"citation_trend":[{"year":2019,"count":1},{"year":2022,"count":1},{"year":2026,"count":1}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#am","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fange.201511711","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/ange.201511711","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ange.201511711","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/am-pdf/10.1002/ange.201511711","host_type":"publisher"},{"url":"https://doi.org/10.1002/ange.201511711","host_type":"journal"}],"fields_of_study":["Electron Spin Resonance Studies","Lanthanide and Transition Metal Complexes","Advanced NMR Techniques and Applications"],"mesh_terms":[],"keywords":["Millisecond","Chemistry","Protein dynamics","Picosecond","Relaxation (psychology)","Magnetization transfer","Saturation (graph theory)","Chemical shift","Biological system","Analytical Chemistry (journal)","Dynamics (music)","Molecular dynamics","Chemical physics","Nuclear magnetic resonance","Computational chemistry","Physical chemistry","Physics"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T04:31:27.582370Z","pmid":null,"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":[]}