{"doi":"10.1126/science.abc0881","title":"Expanding the space of protein geometries by computational design of de novo fold families","abstract":"Naturally occurring proteins vary the precise geometries of structural elements to create distinct shapes optimal for function. We present a computational design method, loop-helix-loop unit combinatorial sampling (LUCS), that mimics nature's ability to create families of proteins with the same overall fold but precisely tunable geometries. Through near-exhaustive sampling of loop-helix-loop elements, LUCS generates highly diverse geometries encompassing those found in nature but also surpassing known structure space. Biophysical characterization showed that 17 (38%) of 45 tested LUCS designs encompassing two different structural topologies were well folded, including 16 with designed non-native geometries. Four experimentally solved structures closely matched the designs. LUCS greatly expands the designable structure space and offers a new paradigm for designing proteins with tunable geometries that may be customizable for novel functions.","journal":"Science","year":2020,"id":57027,"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":81,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"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":227692,"name":"Michael C. Thompson","orcid":"0000-0002-6099-2027","position":1,"is_corresponding":false},{"id":237511,"name":"Sunny Zhang","orcid":"0000-0002-7497-3206","position":2,"is_corresponding":false},{"id":267624,"name":"Lin Liu","orcid":"0000-0003-1283-1410","position":3,"is_corresponding":false},{"id":63530,"name":"James S. Fraser","orcid":"0000-0002-5080-2859","position":4,"is_corresponding":false},{"id":297512,"name":"Mark J. S. Kelly","orcid":"0000-0003-3209-1018","position":5,"is_corresponding":false},{"id":106697,"name":"Tanja Kortemme","orcid":"0000-0002-8494-680X","position":6,"is_corresponding":false},{"id":297511,"name":"Xingjie Pan","orcid":"0000-0002-0060-4352","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-18T21:06:31.136481Z","pmid":"32855341","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":[]}