{"doi":"10.1101/2020.04.02.022368","title":"Membrane Proteins Have Distinct Fast Internal Motion and Residual Conformational Entropy","abstract":"Abstract For a variety of reasons, the internal motions of integral membrane proteins have largely eluded comprehensive experiential characterization. Here, the fast side chain dynamics of the 7-transmembrane helix protein sensory rhodopsin II and the beta-barrel bacterial outer membrane channel protein W have been characterized in lipid bilayers and detergent micelles by solution NMR relaxation techniques. Though of quite different topologies, both proteins are found to have a similar and striking distribution of methyl-bearing amino acid side chain motion that is independent of membrane mimetic. The methyl-bearing side chains of both proteins, on average, are more dynamic in the ps-ns time regime than any soluble protein characterized to date. Approximately one third of methyl-bearing side chains exhibit extreme rotameric averaging on this timescale. Accordingly, both proteins retain an extraordinary residual conformational entropy in the folded state, which provides a counterbalance to the absence of the hydrophobic effect that normally stabilizes the folded state of water-soluble proteins. Furthermore, the large reservoir of conformational entropy that is observed provides the potential to greatly influence the thermodynamics underlying a plethora of membrane protein functions including ligand binding, allostery and signaling.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":122031,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":533086,"name":"Brian Fuglestad","orcid":"0000-0001-8304-8269","position":1,"is_corresponding":false},{"id":533087,"name":"Henry J. Lessen","orcid":"0000-0002-8764-8859","position":2,"is_corresponding":false},{"id":407282,"name":"Matthew A. Stetz","orcid":"0000-0002-4590-2871","position":3,"is_corresponding":false},{"id":533751,"name":"Danny W. Lin","orcid":null,"position":4,"is_corresponding":false},{"id":408211,"name":"Bryan S. Marques","orcid":null,"position":5,"is_corresponding":false},{"id":361197,"name":"Kushol Gupta","orcid":"0000-0002-7006-2667","position":6,"is_corresponding":false},{"id":290959,"name":"Karen G. Fleming","orcid":"0000-0001-5417-8830","position":7,"is_corresponding":false},{"id":407284,"name":"A. Joshua Wand","orcid":"0000-0001-8341-0782","position":8,"is_corresponding":false},{"id":255548,"name":"Evan S. O’Brien","orcid":"0000-0002-2260-7722","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-18T23:14:46.979435Z","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":[]}