{"doi":"10.1093/nar/gkaf552","title":"Structural heterogeneity and dynamics in the apical stem loop of s2m from SARS-CoV-2 Delta by an integrative NMR spectroscopy and MD simulation approach","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>In structured RNAs, helical elements are often capped by apical loops that are integral structural elements, ranging from 3 to &amp;gt;20 nts of size on average, and display a highly heterogeneous energy landscape profile, rendering structural characterization particularly challenging. We here provide a characterization of the SARS-CoV-2 Delta s2m element containing a highly dynamic nonaloop using an integrative approach of nuclear magnetic resonance spectroscopy (NMR), small angle X-ray scattering (SAXS), and molecular dynamics simulations (MD). We further explored the conformational space in the s2m nonaloop and its transient closing 5′-G-U-3′ base pair by MD simulations weighted by experimental NMR observables, leading to a comprehensive representation of the s2m nonaloop motif. Our deconvolution of the ensemble into conformations and dynamics provides a basis for future ensemble-functional characterization of RNA structures featuring dynamic motifs.</jats:p>","journal":"Nucleic Acids Research","year":2025,"id":624174,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"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":1613396,"name":"Joseph A Makowski","orcid":null,"position":1,"is_corresponding":false},{"id":394819,"name":"Tobias Matzel","orcid":"0009-0008-6024-4062","position":2,"is_corresponding":false},{"id":1613398,"name":"Adam H Kensinger","orcid":null,"position":3,"is_corresponding":false},{"id":1613399,"name":"Alexander Herr","orcid":null,"position":4,"is_corresponding":false},{"id":103923,"name":"Christian Richter","orcid":"0000-0003-4261-4214","position":5,"is_corresponding":false},{"id":1613400,"name":"Hendrik R A Jonker","orcid":null,"position":6,"is_corresponding":false},{"id":247862,"name":"Anna Wacker","orcid":"0000-0001-5892-5661","position":7,"is_corresponding":false},{"id":1613403,"name":"Jeffrey D Evanseck","orcid":null,"position":8,"is_corresponding":false},{"id":247900,"name":"Harald Schwalbe","orcid":"0000-0001-5693-7909","position":9,"is_corresponding":false},{"id":1613395,"name":"Maria A Wirtz Martin","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Structural heterogeneity and dynamics in the apical stem loop of s2m from SARS-CoV-2 Delta by an integrative NMR spectroscopy and MD simulation approach","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>In structured RNAs, helical elements are often capped by apical loops that are integral structural elements, ranging from 3 to &amp;gt;20 nts of size on average, and display a highly heterogeneous energy landscape profile, rendering structural characterization particularly challenging. We here provide a characterization of the SARS-CoV-2 Delta s2m element containing a highly dynamic nonaloop using an integrative approach of nuclear magnetic resonance spectroscopy (NMR), small angle X-ray scattering (SAXS), and molecular dynamics simulations (MD). We further explored the conformational space in the s2m nonaloop and its transient closing 5′-G-U-3′ base pair by MD simulations weighted by experimental NMR observables, leading to a comprehensive representation of the s2m nonaloop motif. Our deconvolution of the ensemble into conformations and dynamics provides a basis for future ensemble-functional characterization of RNA structures featuring dynamic motifs.</jats:p>","is_dataset_classified":null,"base_score":1.791759469228055,"endowment":1.791759469228055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40586311","pmcid":"PMC12207407","openalex_id":"https://openalex.org/W4411782601","authors":[],"funders":[{"funder_name":"German funding agency","grant_id":"SCHW701/27-1 (495006306)","title":null},{"funder_name":"German funding agency","grant_id":"SCHW701/30-1 (537258662)","title":null},{"funder_name":"Major Research Instrumentation","grant_id":"CHE-1726824","title":null},{"funder_name":"BAGs","grant_id":"SAXS990","title":null},{"funder_name":"BAGs","grant_id":"1102","title":null},{"funder_name":"BAGs","grant_id":"1106","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R15 AI191143","title":null},{"funder_name":"state of Hesse","grant_id":"","title":null},{"funder_name":"European Union's Horizon 2020","grant_id":"","title":null},{"funder_name":"European Union’s Horizon 2020","grant_id":"","title":null},{"funder_name":"National Science Foundation","grant_id":"","title":null},{"funder_name":"iNEXT-discovery","grant_id":"","title":null}],"total_grants":12,"fwci":2.0315,"citation_percentile":0.86636343,"influential_citations":0,"citation_trend":[{"year":2025,"count":4},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1093/nar/gkaf552","host_type":"journal"},{"url":"https://doi.org/10.1093/nar/gkaf552","host_type":"publisher"},{"url":"https://academic.oup.com/nar/article-pdf/53/12/gkaf552/63626178/gkaf552.pdf","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40586311","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12207407","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12207407","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12207407?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["RNA and protein synthesis mechanisms","RNA Research and Splicing","Viral Infections and Immunology Research"],"mesh_terms":["COVID-19","SARS-CoV-2","Humans","Magnetic Resonance Spectroscopy","Nucleic Acid Conformation","RNA, Viral","X-Ray Diffraction","Nuclear Magnetic Resonance, Biomolecular","Scattering, Small Angle","Molecular Dynamics Simulation"],"keywords":["Molecular dynamics","Nuclear magnetic resonance spectroscopy","Crystallography","Two-dimensional nuclear magnetic resonance spectroscopy","Biophysics","Biology","Stereochemistry","Chemistry","Computational chemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Affordable and clean energy"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"rfam"},{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T02:58:14.026925Z","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":[]}