{"doi":"10.1101/2024.12.10.627859","title":"Recognizing amino acid sidechains in a medium resolution cryo-electron density map","abstract":"Building an accurate atomic structure model of a protein into a cryo-electron microscopy (cryo-EM) map at worse than 3 Angstrom resolution is difficult. To facilitate this task, we devised a method for assigning the amino acid residue sequence to the backbone fragments traced in an input cryo-EM map (EMSequenceFinder). EMSequenceFinder relies on a Bayesian scoring function for ranking 20 standard amino acid residue types at a given backbone position, based on the fit to a density map, map resolution, and secondary structure propensity. The fit to a density is quantified by a convolutional neural network that was trained on ~5.56 million amino acid residue densities extracted from cryo-EM maps at 3-10 Angstrom resolution and corresponding atomic structure models deposited in the Electron Microscopy Data Bank (EMDB). We benchmarked EMSequenceFinder by predicting the sequences of 58,044 distinct ɑ-helix and β-strand fragments, given the fragment backbone coordinates fitted in their density maps. EMSequenceFinder identifies the correct sequence as the best-scoring sequence in 77.8% of these cases. We also assessed EMSequenceFinder on separate datasets of cryo-EM maps at resolutions from 4 to 6 Å. The accuracy of EMSequenceFinder (63.5%) was better than that of three tested state-of-the-art methods, including findMysequence (45%), ModelAngelo (27%), and sequence_from_map in Phenix (12.9%). We further illustrate EMSequenceFinder by threading the SARS-CoV-2 NSP2 sequence into eight cryo-EM maps at resolutions from 3.7 to 7.0 Angstrom. EMSequenceFinder is implemented in our open-source Integrative Modeling Platform (IMP) program. Thus, it is expected to be helpful for integrative structure modeling based on a cryo-EM map and other information, such as models of protein complex components and chemical crosslinks between them. EMSequenceFinder is available as part of our open source IMP distribution at https://integrativemodeling.org/.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":507456,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1358997,"name":"Vipul Kumar","orcid":"0000-0001-7578-7467","position":1,"is_corresponding":false},{"id":1358998,"name":"Tadej Satler","orcid":"0000-0003-2780-1572","position":2,"is_corresponding":false},{"id":103664,"name":"Ramachandran Rakesh","orcid":"0000-0001-7196-5078","position":3,"is_corresponding":false},{"id":103663,"name":"Daniel J. Saltzberg","orcid":"0000-0001-8641-6194","position":4,"is_corresponding":false},{"id":289623,"name":"Ilan E. Chemmama","orcid":"0000-0002-5657-3516","position":5,"is_corresponding":false},{"id":103661,"name":"Kala Bharath Pilla","orcid":"0000-0002-8327-1687","position":6,"is_corresponding":false},{"id":2404,"name":"Ignacia Echeverria","orcid":"0000-0003-4717-1467","position":7,"is_corresponding":false},{"id":682044,"name":"Benjamin Webb","orcid":"0000-0003-3360-4540","position":8,"is_corresponding":false},{"id":108109,"name":"Meghna Gupta","orcid":"0000-0002-7432-3211","position":9,"is_corresponding":false},{"id":1486,"name":"Kliment A. Verba","orcid":"0000-0002-2238-8590","position":10,"is_corresponding":false},{"id":91660,"name":"Andrej Săli","orcid":"0000-0003-0435-6197","position":11,"is_corresponding":false},{"id":1358996,"name":"Dibyendu Mondal","orcid":"0000-0002-5047-6985","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:11:02.460057Z","pmid":"40654703","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":[]}