{"doi":"10.1126/science.add2187","title":"Robust deep learning–based protein sequence design using ProteinMPNN","abstract":"Although deep learning has revolutionized protein structure prediction, almost all experimentally characterized de novo protein designs have been generated using physically based approaches such as Rosetta. Here, we describe a deep learning-based protein sequence design method, ProteinMPNN, that has outstanding performance in both in silico and experimental tests. On native protein backbones, ProteinMPNN has a sequence recovery of 52.4% compared with 32.9% for Rosetta. The amino acid sequence at different positions can be coupled between single or multiple chains, enabling application to a wide range of current protein design challenges. We demonstrate the broad utility and high accuracy of ProteinMPNN using x-ray crystallography, cryo-electron microscopy, and functional studies by rescuing previously failed designs, which were made using Rosetta or AlphaFold, of protein monomers, cyclic homo-oligomers, tetrahedral nanoparticles, and target-binding proteins.","journal":"Science","year":2022,"id":231548,"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":1912,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9468,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":105703,"name":"Ivan Anishchenko","orcid":"0000-0003-3645-2044","position":1,"is_corresponding":false},{"id":807845,"name":"Nathaniel R. Bennett","orcid":"0000-0001-8590-1454","position":2,"is_corresponding":false},{"id":838650,"name":"Hua Bai","orcid":"0000-0002-0448-4052","position":3,"is_corresponding":false},{"id":838651,"name":"Robert J. Ragotte","orcid":"0000-0002-6463-1595","position":4,"is_corresponding":false},{"id":552252,"name":"Lukas F. Milles","orcid":"0000-0001-8417-3205","position":5,"is_corresponding":false},{"id":242363,"name":"Basile I. M. Wicky","orcid":"0000-0002-2501-7875","position":6,"is_corresponding":false},{"id":557871,"name":"Alexis Courbet","orcid":"0000-0003-0539-7011","position":7,"is_corresponding":false},{"id":838652,"name":"Robbert J. de Haas","orcid":"0000-0002-7587-9967","position":8,"is_corresponding":false},{"id":818272,"name":"Neville P. Bethel","orcid":"0000-0001-7576-9613","position":9,"is_corresponding":false},{"id":632750,"name":"Philip J. Y. Leung","orcid":"0000-0002-1801-8968","position":10,"is_corresponding":false},{"id":838653,"name":"Timothy F. Huddy","orcid":"0000-0002-5455-416X","position":11,"is_corresponding":false},{"id":245440,"name":"Samuel J. Pellock","orcid":"0000-0002-7557-7985","position":12,"is_corresponding":false},{"id":552249,"name":"Doug Tischer","orcid":"0000-0003-3633-5542","position":13,"is_corresponding":false},{"id":838654,"name":"F. Chan","orcid":"0000-0001-5168-8579","position":14,"is_corresponding":false},{"id":552677,"name":"Brian Koepnick","orcid":"0000-0002-5792-8112","position":15,"is_corresponding":false},{"id":838655,"name":"Hannah Nguyen","orcid":"0000-0001-9696-4004","position":16,"is_corresponding":false},{"id":268184,"name":"Alex Kang","orcid":"0000-0001-5487-0499","position":17,"is_corresponding":false},{"id":249510,"name":"Banumathi Sankaran","orcid":"0000-0002-3266-8131","position":18,"is_corresponding":false},{"id":453451,"name":"Asim K. Bera","orcid":"0000-0001-9473-2912","position":19,"is_corresponding":false},{"id":108915,"name":"Neil P. King","orcid":"0000-0002-2978-4692","position":20,"is_corresponding":false},{"id":105706,"name":"David Baker","orcid":"0000-0001-7896-6217","position":21,"is_corresponding":false},{"id":552413,"name":"Justas Dauparas","orcid":"0000-0002-0030-144X","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T00:20:51.245255Z","pmid":"36108050","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":[]}