{"doi":"10.17615/p7z7-b073","title":"Direct Detection of Structurally Resolved Dynamics in a Multiconformation Receptor−Ligand Complex","abstract":"Structure-based drug design relies on static protein structures despite significant evidence for the need to include protein dynamics as a serious consideration. In practice, dynamic motions are neglected because they are not understood well enough to model – a situation resulting from a lack of explicit experimental examples of dynamic receptor-ligand complexes. Here, we report high-resolution details of pronounced ~1 ms timescale motions of a receptor-small molecule complex using a combination of NMR and X-ray crystallography. Large conformational dynamics in Escherichia coli dihydrofolate reductase are driven by internal switching motions of the drug-like, nanomolar-affinity inhibitor. Carr-Purcell-Meiboom-Gill relaxation dispersion experiments and NOEs revealed the crystal structure to contain critical elements of the high energy protein-ligand conformation. The availability of accurate, structurally resolved dynamics in a protein-ligand complex should serve as a valuable benchmark for modeling dynamics in other receptor-ligand complexes and prediction of binding affinities.","journal":"Figshare","year":2021,"id":231070,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9462,"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":838016,"name":"Hao Tang","orcid":"0000-0003-2202-0515","position":1,"is_corresponding":false},{"id":280535,"name":"Ashutosh Tripathy","orcid":"0000-0001-9922-735X","position":2,"is_corresponding":false},{"id":591927,"name":"Keith R. Miller","orcid":"0000-0003-0105-2454","position":3,"is_corresponding":false},{"id":609289,"name":"Anna V. Gromova","orcid":null,"position":4,"is_corresponding":false},{"id":517628,"name":"Scott F. Singleton","orcid":"0000-0001-8797-4438","position":5,"is_corresponding":false},{"id":149321,"name":"Andrew L. Lee","orcid":"0000-0003-2783-1907","position":6,"is_corresponding":false},{"id":609290,"name":"M.J. Carroll","orcid":null,"position":7,"is_corresponding":false},{"id":594873,"name":"Edward J. Collins","orcid":"0000-0002-3523-8532","position":8,"is_corresponding":false},{"id":602350,"name":"Xiang Simon Wang","orcid":"0000-0002-4156-3753","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:55:12.400773Z","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":[]}