{"doi":"10.1002/prot.22429","title":"Beyond the Twilight Zone: Automated prediction of structural properties of proteins by recursive neural networks and remote homology information","abstract":"<jats:title>Abstract</jats:title><jats:p>The prediction of 1D structural properties of proteins is an important step toward the prediction of protein structure and function, not only in the <jats:italic>ab initio</jats:italic> case but also when homology information to known structures is available. Despite this the vast majority of 1D predictors do not incorporate homology information into the prediction process. We develop a novel structural alignment method, SAMD, which we use to build alignments of putative remote homologues that we compress into templates of structural frequency profiles. We use these templates as additional input to ensembles of recursive neural networks, which we specialise for the prediction of query sequences that show only remote homology to any Protein Data Bank structure. We predict four 1D structural properties – secondary structure, relative solvent accessibility, backbone structural motifs, and contact density. Secondary structure prediction accuracy, tested by five‐fold cross‐validation on a large set of proteins allowing less than 25% sequence identity between training and test set and query sequences and templates, exceeds 82%, outperforming its <jats:italic>ab initio</jats:italic> counterpart, other state‐of‐the‐art secondary structure predictors (Jpred 3 and PSIPRED) and two other systems based on PSI‐BLAST and COMPASS templates. We show that structural information from homologues improves prediction accuracy well beyond the Twilight Zone of sequence similarity, even below 5% sequence identity, for all four structural properties. Significant improvement over the extraction of structural information directly from PDB templates suggests that the combination of sequence and template information is more informative than templates alone. Proteins 2009. © 2009 Wiley‐Liss, Inc.</jats:p>","journal":"Proteins: Structure, Function, and Bioinformatics","year":2009,"id":40012,"datarank":2.109513726625478,"base_score":4.060443010546419,"endowment":4.060443010546419,"self_citation_contribution":0.6090664515819629,"citation_network_contribution":1.5004472750435154,"self_endowment_contribution":0.6090664515819629,"citer_contribution":1.5004472750435154,"corpus_percentile":null,"corpus_rank":null,"citation_count":57,"citer_count":37,"citers_with_citation_signal":30,"citers_with_endowment":30,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":195181,"name":"Gianluca Pollastri","orcid":null,"position":1,"is_corresponding":false},{"id":195180,"name":"Catherine Mooney","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.060443010546419,"endowment":4.060443010546419,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19422056","pmcid":null,"openalex_id":"https://openalex.org/W2066914088","authors":[],"funders":[{"funder_name":"UCD President's Award 2004","grant_id":"05/RFP/CMS0029","title":null},{"funder_name":"UCD President's Award 2004","grant_id":"RP/2005/219","title":null},{"funder_name":"Health Research Board of Ireland","grant_id":"","title":null}],"total_grants":3,"fwci":2.7378,"citation_percentile":0.90359119,"influential_citations":1,"citation_trend":[{"year":2012,"count":4},{"year":2013,"count":8},{"year":2014,"count":4},{"year":2015,"count":5},{"year":2017,"count":3},{"year":2018,"count":4},{"year":2019,"count":7},{"year":2020,"count":2},{"year":2021,"count":1},{"year":2025,"count":1},{"year":2026,"count":2}],"oa_status":"green","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"http://hdl.handle.net/10197/3442","host_type":"repository"},{"url":"http://researchrepository.ucd.ie/bitstreams/44b100ad-9c1b-417f-8e39-1eacc244b0ba/download","host_type":"GREEN"},{"url":"http://hdl.handle.net/10197/3442","host_type":"repository"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fprot.22429","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/prot.22429","host_type":"publisher"},{"url":"https://doi.org/10.1002/prot.22429","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/19422056","host_type":"repository"}],"fields_of_study":["Protein Structure and Dynamics","Computational Drug Discovery Methods","Enzyme Structure and Function","Computer Science","Medicine","Biology","Amino Acid Sequence","Computational Biology","Databases, Protein","Protein Structure, Secondary","Proteins","Sequence Analysis, Protein","Sequence Homology, Amino Acid"],"mesh_terms":["Amino Acid Sequence","Proteins","Sequence Homology, Amino Acid","Protein Structure, Secondary","Computational Biology","Sequence Analysis, Protein","Databases, Protein"],"keywords":["Template","Structural alignment","Computer science","Protein structure database","Structural similarity","Protein Data Bank (RCSB PDB)","Protein structure prediction","Structural Classification of Proteins database","Structural bioinformatics","Protein secondary structure","Protein structure","Homology (biology)","Homology modeling","Artificial intelligence","Structural motif","Sequence homology","Computational biology","Sequence alignment","Peptide sequence","Biology","Genetics","Sequence database","Amino acid"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-12T00:24:01.782044Z","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":[]}