{"doi":"10.1073/pnas.2220380120","title":"De novo designed ice-binding proteins from twist-constrained helices","abstract":"Attaining molecular-level control over solidification processes is a crucial aspect of materials science. To control ice formation, organisms have evolved bewildering arrays of ice-binding proteins (IBPs), but these have poorly understood structure-activity relationships. We propose that reverse engineering using de novo computational protein design can shed light on structure-activity relationships of IBPs. We hypothesized that the model alpha-helical winter flounder antifreeze protein uses an unusual undertwisting of its alpha-helix to align its putative ice-binding threonine residues in exactly the same direction. We test this hypothesis by designing a series of straight three-helix bundles with an ice-binding helix projecting threonines and two supporting helices constraining the twist of the ice-binding helix. Our findings show that ice-recrystallization inhibition by the designed proteins increases with the degree of designed undertwisting, thus validating our hypothesis, and opening up avenues for the computational design of IBPs.","journal":"Proceedings of the National Academy of Sciences","year":2023,"id":347997,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1011785,"name":"Roderick P. Tas","orcid":"0000-0003-3111-8784","position":1,"is_corresponding":false},{"id":1012321,"name":"Daniëlle van den Broek","orcid":null,"position":2,"is_corresponding":false},{"id":1089862,"name":"Chuanbao Zheng","orcid":"0000-0002-0866-9839","position":3,"is_corresponding":false},{"id":838655,"name":"Hannah Nguyen","orcid":"0000-0001-9696-4004","position":4,"is_corresponding":false},{"id":268184,"name":"Alex Kang","orcid":"0000-0001-5487-0499","position":5,"is_corresponding":false},{"id":453451,"name":"Asim K. Bera","orcid":"0000-0001-9473-2912","position":6,"is_corresponding":false},{"id":108915,"name":"Neil P. King","orcid":"0000-0002-2978-4692","position":7,"is_corresponding":false},{"id":318153,"name":"Ilja K. Voets","orcid":"0000-0003-3543-4821","position":8,"is_corresponding":false},{"id":1011786,"name":"Renko de Vries","orcid":"0000-0001-8664-3135","position":9,"is_corresponding":false},{"id":838652,"name":"Robbert J. de Haas","orcid":"0000-0002-7587-9967","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T01:12:01.859977Z","pmid":"37364125","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":[]}