{"doi":"10.1101/2025.07.03.663071","title":"Multimodal deep learning integration of cryo-EM and AlphaFold3 for high-accuracy protein structure determination","abstract":"Cryo-electron microscopy (cryo-EM) is a key technology for determining the structures of proteins, particularly large protein complexes. However, automatically building high-accuracy protein structures from cryo-EM density maps remains a crucial challenge. In this work, we introduce MICA, a fully automatic and multimodal deep learning approach combining cryo-EM density maps with AlphaFold3-predicted structures at both input and output levels to improve cryo-EM protein structure modeling. It first uses a multi-task encoder-decoder architecture with a feature pyramid network to predict backbone atoms, Cα atoms and amino acid types from both cryo-EM maps and AlphaFold3-predicted structures, which are used to build an initial backbone model. This model is further refined using AlphaFold3-predicted structures and density maps to build final atomic structures. MICA significantly outperforms other state-of-the-art deep learning methods in terms of both modeling accuracy and completeness and is robust to protein size and map resolution. Additionally, it builds high-accuracy structural models with an average template-based modeling score (TM-score) of 0.93 from recently released high-resolution cryo-EM density maps, showing it can be used for real-world, automated, accurate protein structure determination.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":555237,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9586,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1162213,"name":"Ashwin Dhakal","orcid":"0000-0002-4047-9947","position":1,"is_corresponding":false},{"id":236517,"name":"Jianlin Cheng","orcid":"0000-0003-0305-2853","position":2,"is_corresponding":false},{"id":1162212,"name":"Rajan Gyawali","orcid":"0000-0002-7052-4964","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T02:54:59.329539Z","pmid":"40631196","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":[]}