{"id":"https://openalex.org/W4415192809","doi":"https://doi.org/10.1109/jbhi.2025.3620163","title":"HighMPNN: A Graph Neural Network Approach for Structure-Constrained Cyclic Peptide Sequence Design","display_name":"HighMPNN: A Graph Neural Network Approach for Structure-Constrained Cyclic Peptide Sequence Design","publication_year":2025,"publication_date":"2025-10-13","ids":{"openalex":"https://openalex.org/W4415192809","doi":"https://doi.org/10.1109/jbhi.2025.3620163","pmid":"https://pubmed.ncbi.nlm.nih.gov/41082435"},"language":"en","primary_location":{"id":"doi:10.1109/jbhi.2025.3620163","is_oa":false,"landing_page_url":"https://doi.org/10.1109/jbhi.2025.3620163","pdf_url":null,"source":{"id":"https://openalex.org/S2495854775","display_name":"IEEE Journal of Biomedical and Health Informatics","issn_l":"2168-2194","issn":["2168-2194","2168-2208"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310319808","host_organization_name":"Institute of Electrical and Electronics Engineers","host_organization_lineage":["https://openalex.org/P4310319808"],"host_organization_lineage_names":["Institute of Electrical and Electronics Engineers"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"IEEE Journal of Biomedical and Health Informatics","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5113898773","display_name":"Wen Xu","orcid":"https://orcid.org/0009-0007-2656-0988"},"institutions":[{"id":"https://openalex.org/I55712492","display_name":"Zhejiang University of Technology","ror":"https://ror.org/02djqfd08","country_code":"CN","type":"education","lineage":["https://openalex.org/I55712492"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Wen Xu","raw_affiliation_strings":["College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, China"],"raw_orcid":"https://orcid.org/0009-0007-2656-0988","affiliations":[{"raw_affiliation_string":"College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, China","institution_ids":["https://openalex.org/I55712492"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5102819904","display_name":"Chengyun Zhang","orcid":"https://orcid.org/0000-0002-8499-5273"},"institutions":[{"id":"https://openalex.org/I4210145183","display_name":"Shenzhen Baoan High School Group","ror":"https://ror.org/03fxa2376","country_code":"CN","type":"education","lineage":["https://openalex.org/I4210145183"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Chengyun Zhang","raw_affiliation_strings":["AI Department, Shenzhen Highslab Therapeutics Inc., Shenzhen, China"],"raw_orcid":"https://orcid.org/0000-0002-8499-5273","affiliations":[{"raw_affiliation_string":"AI Department, Shenzhen Highslab Therapeutics Inc., Shenzhen, China","institution_ids":["https://openalex.org/I4210145183"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5026019153","display_name":"Tianfeng Shang","orcid":null},"institutions":[{"id":"https://openalex.org/I4210145183","display_name":"Shenzhen Baoan High School Group","ror":"https://ror.org/03fxa2376","country_code":"CN","type":"education","lineage":["https://openalex.org/I4210145183"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Tianfeng Shang","raw_affiliation_strings":["AI Department, Shenzhen Highslab Therapeutics Inc., Shenzhen, China"],"raw_orcid":"https://orcid.org/0009-0002-0307-4585","affiliations":[{"raw_affiliation_string":"AI Department, Shenzhen Highslab Therapeutics Inc., Shenzhen, China","institution_ids":["https://openalex.org/I4210145183"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5101349273","display_name":"Qingyi Mao","orcid":null},"institutions":[{"id":"https://openalex.org/I55712492","display_name":"Zhejiang University of Technology","ror":"https://ror.org/02djqfd08","country_code":"CN","type":"education","lineage":["https://openalex.org/I55712492"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Qingyi Mao","raw_affiliation_strings":["College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, China"],"raw_orcid":"https://orcid.org/0009-0009-8548-1221","affiliations":[{"raw_affiliation_string":"College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, China","institution_ids":["https://openalex.org/I55712492"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5008112425","display_name":"Jingjing Guo","orcid":"https://orcid.org/0000-0002-4632-4364"},"institutions":[{"id":"https://openalex.org/I49835588","display_name":"Macao Polytechnic University","ror":"https://ror.org/02sf5td35","country_code":"MO","type":"education","lineage":["https://openalex.org/I49835588"]}],"countries":["MO"],"is_corresponding":false,"raw_author_name":"Jingjing Guo","raw_affiliation_strings":["Faculty of Applied Sciences, Macao Polytechnic University, Macao, China"],"raw_orcid":"https://orcid.org/0000-0002-4632-4364","affiliations":[{"raw_affiliation_string":"Faculty of Applied Sciences, Macao Polytechnic University, Macao, China","institution_ids":["https://openalex.org/I49835588"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5017761454","display_name":"Hongliang Duan","orcid":"https://orcid.org/0000-0002-9194-0115"},"institutions":[{"id":"https://openalex.org/I49835588","display_name":"Macao Polytechnic University","ror":"https://ror.org/02sf5td35","country_code":"MO","type":"education","lineage":["https://openalex.org/I49835588"]}],"countries":["MO"],"is_corresponding":false,"raw_author_name":"Hongliang Duan","raw_affiliation_strings":["Faculty of Applied Sciences, Macao Polytechnic University, Macao, China"],"raw_orcid":"https://orcid.org/0000-0002-9194-0115","affiliations":[{"raw_affiliation_string":"Faculty of Applied Sciences, Macao Polytechnic University, Macao, China","institution_ids":["https://openalex.org/I49835588"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":6,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":0.576,"has_fulltext":false,"cited_by_count":1,"citation_normalized_percentile":{"value":0.71277673,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":95,"max":98},"biblio":{"volume":"30","issue":"5","first_page":"3960","last_page":"3970"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12254","display_name":"Machine Learning in Bioinformatics","score":0.960099995136261,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T12254","display_name":"Machine Learning in Bioinformatics","score":0.960099995136261,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10911","display_name":"Chemical Synthesis and Analysis","score":0.9298999905586243,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/sequence","display_name":"Sequence (biology)","score":0.6661999821662903},{"id":"https://openalex.org/keywords/cyclic-peptide","display_name":"Cyclic peptide","score":0.5389000177383423},{"id":"https://openalex.org/keywords/artificial-neural-network","display_name":"Artificial neural network","score":0.5231000185012817},{"id":"https://openalex.org/keywords/graph","display_name":"Graph","score":0.4674000144004822},{"id":"https://openalex.org/keywords/consistency","display_name":"Consistency (knowledge bases)","score":0.4586000144481659},{"id":"https://openalex.org/keywords/peptide-sequence","display_name":"Peptide sequence","score":0.42250001430511475},{"id":"https://openalex.org/keywords/peptide","display_name":"Peptide","score":0.41690000891685486},{"id":"https://openalex.org/keywords/sequence-alignment","display_name":"Sequence alignment","score":0.3531000018119812}],"concepts":[{"id":"https://openalex.org/C2778112365","wikidata":"https://www.wikidata.org/wiki/Q3511065","display_name":"Sequence (biology)","level":2,"score":0.6661999821662903},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.609000027179718},{"id":"https://openalex.org/C60984968","wikidata":"https://www.wikidata.org/wiki/Q389172","display_name":"Cyclic peptide","level":3,"score":0.5389000177383423},{"id":"https://openalex.org/C50644808","wikidata":"https://www.wikidata.org/wiki/Q192776","display_name":"Artificial neural network","level":2,"score":0.5231000185012817},{"id":"https://openalex.org/C132525143","wikidata":"https://www.wikidata.org/wiki/Q141488","display_name":"Graph","level":2,"score":0.4674000144004822},{"id":"https://openalex.org/C2776436953","wikidata":"https://www.wikidata.org/wiki/Q5163215","display_name":"Consistency (knowledge bases)","level":2,"score":0.4586000144481659},{"id":"https://openalex.org/C11413529","wikidata":"https://www.wikidata.org/wiki/Q8366","display_name":"Algorithm","level":1,"score":0.45509999990463257},{"id":"https://openalex.org/C167625842","wikidata":"https://www.wikidata.org/wiki/Q899763","display_name":"Peptide sequence","level":3,"score":0.42250001430511475},{"id":"https://openalex.org/C2779281246","wikidata":"https://www.wikidata.org/wiki/Q172847","display_name":"Peptide","level":2,"score":0.41690000891685486},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.3808000087738037},{"id":"https://openalex.org/C45484198","wikidata":"https://www.wikidata.org/wiki/Q827246","display_name":"Sequence alignment","level":4,"score":0.3531000018119812},{"id":"https://openalex.org/C88230418","wikidata":"https://www.wikidata.org/wiki/Q131476","display_name":"Graph theory","level":2,"score":0.3328000009059906},{"id":"https://openalex.org/C108583219","wikidata":"https://www.wikidata.org/wiki/Q197536","display_name":"Deep learning","level":2,"score":0.3287000060081482},{"id":"https://openalex.org/C28719098","wikidata":"https://www.wikidata.org/wiki/Q44946","display_name":"Point (geometry)","level":2,"score":0.3244999945163727},{"id":"https://openalex.org/C192209626","wikidata":"https://www.wikidata.org/wiki/Q190909","display_name":"Focus (optics)","level":2,"score":0.3199000060558319},{"id":"https://openalex.org/C80444323","wikidata":"https://www.wikidata.org/wiki/Q2878974","display_name":"Theoretical computer science","level":1,"score":0.30790001153945923},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.30140000581741333},{"id":"https://openalex.org/C184720557","wikidata":"https://www.wikidata.org/wiki/Q7825049","display_name":"Topology (electrical circuits)","level":2,"score":0.2976999878883362},{"id":"https://openalex.org/C126042441","wikidata":"https://www.wikidata.org/wiki/Q1324888","display_name":"Frame (networking)","level":2,"score":0.29269999265670776},{"id":"https://openalex.org/C4668613","wikidata":"https://www.wikidata.org/wiki/Q4116110","display_name":"Structural alignment","level":5,"score":0.27059999108314514},{"id":"https://openalex.org/C155032097","wikidata":"https://www.wikidata.org/wiki/Q798503","display_name":"Backpropagation","level":3,"score":0.2531999945640564},{"id":"https://openalex.org/C32946077","wikidata":"https://www.wikidata.org/wiki/Q618079","display_name":"Network analysis","level":2,"score":0.25}],"mesh":[{"descriptor_ui":"D000077321","descriptor_name":"Deep Learning","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000098422","descriptor_name":"Graph Neural Networks","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000595","descriptor_name":"Amino Acid Sequence","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D010456","descriptor_name":"Peptides, Cyclic","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D016571","descriptor_name":"Neural Networks, Computer","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D020539","descriptor_name":"Sequence Analysis, Protein","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1109/jbhi.2025.3620163","is_oa":false,"landing_page_url":"https://doi.org/10.1109/jbhi.2025.3620163","pdf_url":null,"source":{"id":"https://openalex.org/S2495854775","display_name":"IEEE Journal of Biomedical and Health Informatics","issn_l":"2168-2194","issn":["2168-2194","2168-2208"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310319808","host_organization_name":"Institute of Electrical and Electronics Engineers","host_organization_lineage":["https://openalex.org/P4310319808"],"host_organization_lineage_names":["Institute of Electrical and Electronics Engineers"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"IEEE Journal of Biomedical and Health Informatics","raw_type":"journal-article"},{"id":"pmid:41082435","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/41082435","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"IEEE journal of biomedical and health informatics","raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[],"awards":[{"id":"https://openalex.org/G7287413255","display_name":null,"funder_award_id":"0151/2024/RIA2","funder_id":"https://openalex.org/F4320323893","funder_display_name":"Fundo para o Desenvolvimento das Ci\u00eancias e da Tecnologia"}],"funders":[{"id":"https://openalex.org/F4320323893","display_name":"Fundo para o Desenvolvimento das Ci\u00eancias e da Tecnologia","ror":"https://ror.org/05vna4324"}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":[],"abstract_inverted_index":{"Cyclic":[0],"peptides":[1,27],"become":[2],"attractive":[3],"therapeutic":[4],"candidates":[5],"due":[6],"to":[7,99,121,148,161,173],"their":[8],"diverse":[9,179],"biological":[10],"activities.":[11],"However,":[12],"existing":[13],"deep":[14],"learning-based":[15],"sequence":[16,59,82,102,114,127],"design":[17],"models,":[18,123],"such":[19],"as":[20],"ProteinMPNN,":[21],"are":[22],"primarily":[23],"intended":[24],"for":[25,35,56],"linear":[26],"or":[28],"proteins":[29],"and":[30,104,117,132,177,188],"do":[31],"not":[32],"explicitly":[33],"account":[34],"the":[36,62,69,74,97,145,171],"unique":[37],"topological":[38],"constraints":[39,67],"of":[40,64,77,86,130,139],"cyclic":[41,57,78,180,185],"peptides.":[42],"In":[43],"this":[44],"study,":[45],"we":[46],"introduce":[47],"HighMPNN,":[48],"a":[49],"graph":[50],"neural":[51],"network":[52],"model":[53,98],"specifically":[54],"developed":[55],"peptide":[58,181,186],"design.":[60],"Through":[61],"integration":[63],"explicit":[65],"structural":[66,106,118],"into":[68],"GNN-based":[70],"framework,":[71],"HighMPNN":[72,108,158],"captures":[73],"geometric":[75],"features":[76],"backbones":[79],"while":[80],"learning":[81],"patterns.":[83],"The":[84],"combination":[85],"cross-entropy":[87],"loss":[88,95],"with":[89],"Frame":[90],"Aligned":[91],"Point":[92],"Error":[93],"(FAPE)":[94],"allows":[96],"simultaneously":[100],"optimize":[101],"generation":[103],"enhance":[105],"accuracy.":[107],"demonstrates":[109],"superior":[110],"performance":[111],"in":[112],"both":[113],"recovery":[115,128],"rate":[116,129],"consistency":[119],"compared":[120],"baseline":[122],"achieving":[124],"an":[125,133],"average":[126,134],"63.95%":[131],"C\u03b1":[135],"root-mean-square":[136],"deviation":[137],"(RMSD_C\u03b1)":[138],"1.413":[140],"\u00c5.":[141],"These":[142],"results":[143],"highlight":[144],"model's":[146],"ability":[147],"generate":[149],"sequences":[150],"that":[151],"closely":[152],"resemble":[153],"native":[154],"backbones.":[155],"At":[156],"present,":[157],"is":[159],"limited":[160],"natural":[162],"amino":[163],"acids.":[164],"Future":[165],"work":[166],"will":[167],"focus":[168],"on":[169],"extending":[170],"framework":[172],"support":[174],"non-canonical":[175],"residues":[176],"structurally":[178],"scaffolds,":[182],"thereby":[183],"accelerating":[184],"discovery":[187],"advancing":[189],"peptide-based":[190],"drug":[191],"development.":[192]},"counts_by_year":[{"year":2026,"cited_by_count":1}],"updated_date":"2026-06-11T09:08:48.828518","created_date":"2025-10-15T00:00:00"}
