{"doi":"10.1002/cbic.202500085","title":"Effects of D‐Amino Acid Replacements on the Conformational Stability of Miniproteins","abstract":"For many proteins, proper function requires adoption of a specific tertiary structure. This study explores the effects of L-to-D amino acid substitutions on tertiary structure stability for two well-known miniproteins, a single-site variant of the chicken villin headpiece subdomain (VHP) and the human Pin1 WW domain (WW). For VHP, which features an α-helix-rich tertiary structure, substitutions led to significant destabilization, as detected by variable temperature circular dichroism (CD) measurements. For WW, which has a β-sheet-rich tertiary structure, most single L-to-D changes seemed to cause complete unfolding at room temperature, according to CD measurements. These findings suggest that amino acid residue configuration changes at a single site will often prove to be deleterious in terms of tertiary structure stability, and in some cases dramatically destabilizing.","journal":"ChemBioChem","year":2025,"id":533271,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1415166,"name":"Jiawen Huang","orcid":"0009-0009-3958-529X","position":1,"is_corresponding":false},{"id":676878,"name":"Ariel J. Kuhn","orcid":"0000-0003-1535-8614","position":2,"is_corresponding":false},{"id":294605,"name":"Samuel H. Gellman","orcid":"0000-0001-5617-0058","position":3,"is_corresponding":false},{"id":292746,"name":"Ruiwen Xu","orcid":"0000-0001-8477-2718","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T02:51:32.301795Z","pmid":"39948034","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":[]}