{"doi":"10.1101/2024.01.20.576370","title":"DiffModeler: Large Macromolecular Structure Modeling in Low-Resolution Cryo-EM Maps Using Diffusion Model","abstract":"Cryogenic electron microscopy (cryo-EM) has now been widely used for determining multi-chain protein complexes. However, modeling a complex structure is challenging particularly when the map resolution is low, typically in the intermediate resolution range of 5 to 10 Å. Within this resolution range, even accurate structure fitting is difficult, let alone de novo modeling. To address this challenge, here we present DiffModeler, a fully automated method for modeling protein complex structures. DiffModeler employs a diffusion model for backbone tracing and integrates AlphaFold2-predicted single-chain structures for structure fitting. Extensive testing on cryo-EM maps at intermediate resolutions demonstrates the exceptional accuracy of DiffModeler in structure modeling, achieving an average TM-Score of 0.92, surpassing existing methodologies significantly. Notably, DiffModeler successfully modeled a protein complex composed of 47 chains and 13,462 residues, achieving a high TM-Score of 0.94. Further benchmarking at low resolutions (10-20 Å confirms its versatility, demonstrating plausible performance. Moreover, when coupled with CryoREAD, DiffModeler excels in constructing protein-DNA/RNA complex structures for near-atomic resolution maps (0-5 Å), showcasing state-of-the-art performance with average TM-Scores of 0.88 and 0.91 across two datasets.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":484500,"datarank":0.5433665057152828,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.19797874176617591,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.19797874176617591,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":8,"citers_with_citation_signal":6,"citers_with_endowment":6,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"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":590416,"name":"Zhu Han","orcid":"0000-0002-6606-5822","position":1,"is_corresponding":false},{"id":558774,"name":"Genki Terashi","orcid":"0000-0002-5339-909X","position":2,"is_corresponding":false},{"id":1326668,"name":"Manav Taluja","orcid":"0009-0005-1263-4224","position":3,"is_corresponding":false},{"id":316939,"name":"Daisuke Kihara","orcid":"0000-0003-4091-6614","position":4,"is_corresponding":false},{"id":542642,"name":"Xiao Wang","orcid":"0000-0003-4435-7098","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:07:42.971417Z","pmid":"38328203","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":[]}