{"doi":"10.1073/pnas.2112021118","title":"Atomic view of cosolute-induced protein denaturation probed by NMR solvent paramagnetic relaxation enhancement","abstract":"The system studied is the metastable drkN SH3 domain, which exists in dynamic equilibrium between native and unfolded states, thereby permitting us to probe the interactions of cosolutes with both states simultaneously under the same conditions. Two paramagnetic cosolute denaturants were investigated, one neutral and the other negatively charged, differing in the presence of a carboxyamide group versus a carboxylate. Our results demonstrate that attractive cosolute-protein backbone interactions occur largely in the unfolded state and some loop regions in the native state, electrostatic interactions reduce the [Formula: see text] values, and temperature predominantly impacts interactions with the unfolded state. Thus, destabilization of the native state in this instance arises predominantly as a consequence of interactions of the cosolutes with the unfolded state.","journal":"Proceedings of the National Academy of Sciences","year":2021,"id":177643,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":458318,"name":"Janghyun Yoo","orcid":"0000-0002-2330-4053","position":1,"is_corresponding":false},{"id":298285,"name":"Charles D. Schwieters","orcid":"0000-0002-4216-4658","position":2,"is_corresponding":false},{"id":274346,"name":"Robert B. Best","orcid":"0000-0002-7893-3543","position":3,"is_corresponding":false},{"id":318461,"name":"Hoi Sung Chung","orcid":"0000-0001-6897-4969","position":4,"is_corresponding":false},{"id":57566,"name":"G. Marius Clore","orcid":"0000-0003-3809-1027","position":5,"is_corresponding":false},{"id":317919,"name":"Yusuke Okuno","orcid":"0000-0003-3139-9272","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T23:47:32.096934Z","pmid":"34404723","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":[]}