{"id":"https://openalex.org/W7222950704","doi":"https://doi.org/10.64898/2026.10.17.759831","title":"Network organization of protein binding-site landscapes across scales","display_name":"Network organization of protein binding-site landscapes across scales","publication_year":2026,"publication_date":"2026-10-19","ids":{"openalex":"https://openalex.org/W7222950704","doi":"https://doi.org/10.64898/2026.10.17.759831"},"language":"en","primary_location":{"id":"doi:10.64898/2026.10.17.759831","doi":"https://doi.org/10.64898/2026.10.17.759831","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.17.759831","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/19/2026.10.17.759831.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/19/2026.10.17.759831.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5159060412","display_name":"Gonzalo Javier Giordano","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I151201029","display_name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","ror":"https://ror.org/03cqe8w59","country_code":"AR","type":"government","lineage":["https://openalex.org/I151201029","https://openalex.org/I4210123736","https://openalex.org/I4387155568"]},{"id":"https://openalex.org/I24354313","display_name":"Universidad de Buenos Aires","ror":"https://ror.org/0081fs513","country_code":"AR","type":"education","lineage":["https://openalex.org/I24354313"]},{"id":"https://openalex.org/I2801749607","display_name":"Fundaci\u00f3n Instituto Leloir","ror":"https://ror.org/0431v7h69","country_code":"AR","type":"facility","lineage":["https://openalex.org/I2801749607"]}],"countries":["AR"],"is_corresponding":false,"raw_author_name":"G. Giordano","raw_affiliation_strings":["Dept. de F\u00edsica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina","Instituto de Investigaciones Bioqu\u00edmicas de Buenos Aires (IIBBA) \u2013 CONICET, Argentina","Laboratorio de Biologia de Sistemas Integrativa, Fundacion Instituto Leloir, Buenos Aires, Argentina"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Dept. de F\u00edsica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina","institution_ids":["https://openalex.org/I24354313"]},{"raw_affiliation_string":"Instituto de Investigaciones Bioqu\u00edmicas de Buenos Aires (IIBBA) \u2013 CONICET, Argentina","institution_ids":["https://openalex.org/I151201029"]},{"raw_affiliation_string":"Laboratorio de Biologia de Sistemas Integrativa, Fundacion Instituto Leloir, Buenos Aires, Argentina","institution_ids":["https://openalex.org/I2801749607"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5005988020","display_name":"Ariel Chernomoretz","orcid":"https://orcid.org/0000-0003-2675-353X","observed_orcids":["https://orcid.org/0000-0003-2675-353X"]},"institutions":[{"id":"https://openalex.org/I151201029","display_name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","ror":"https://ror.org/03cqe8w59","country_code":"AR","type":"government","lineage":["https://openalex.org/I151201029","https://openalex.org/I4210123736","https://openalex.org/I4387155568"]},{"id":"https://openalex.org/I24354313","display_name":"Universidad de Buenos Aires","ror":"https://ror.org/0081fs513","country_code":"AR","type":"education","lineage":["https://openalex.org/I24354313"]},{"id":"https://openalex.org/I2801749607","display_name":"Fundaci\u00f3n Instituto Leloir","ror":"https://ror.org/0431v7h69","country_code":"AR","type":"facility","lineage":["https://openalex.org/I2801749607"]}],"countries":["AR"],"is_corresponding":true,"raw_author_name":"A. Chernomoretz","raw_affiliation_strings":["Dept. de F\u00edsica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina","Instituto de F\u00edsica Interdisciplinaria y Aplicada (INFINA), UBA-CONICET, Argentina","Laboratorio de Biologia de Sistemas Integrativa, Fundacion Instituto Leloir, Buenos Aires, Argentina"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Dept. de F\u00edsica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina","institution_ids":["https://openalex.org/I24354313"]},{"raw_affiliation_string":"Instituto de F\u00edsica Interdisciplinaria y Aplicada (INFINA), UBA-CONICET, Argentina","institution_ids":["https://openalex.org/I151201029","https://openalex.org/I24354313"]},{"raw_affiliation_string":"Laboratorio de Biologia de Sistemas Integrativa, Fundacion Instituto Leloir, Buenos Aires, Argentina","institution_ids":["https://openalex.org/I2801749607"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5005988020"],"corresponding_institution_ids":["https://openalex.org/I151201029","https://openalex.org/I24354313","https://openalex.org/I2801749607"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.9175000190734863,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.9175000190734863,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.04430000111460686,"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/T12254","display_name":"Machine Learning in Bioinformatics","score":0.030500000342726707,"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/protein-binding-sites","display_name":"protein binding sites","score":0.996999979019165},{"id":"https://openalex.org/keywords/ligand-recognition","display_name":"ligand recognition","score":0.7760000228881836},{"id":"https://openalex.org/keywords/protein-language-model-embeddings","display_name":"protein language model embeddings","score":0.7580000162124634},{"id":"https://openalex.org/keywords/prott5","display_name":"ProtT5","score":0.9879999756813049},{"id":"https://openalex.org/keywords/community-structure","display_name":"community structure","score":0.6269999742507935},{"id":"https://openalex.org/keywords/kinases","display_name":"kinases","score":0.8149999976158142},{"id":"https://openalex.org/keywords/drug-repurposing","display_name":"drug repurposing","score":0.9639999866485596},{"id":"https://openalex.org/keywords/ligand-selectivity","display_name":"ligand selectivity","score":0.722000002861023}],"concepts":[{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.5012000203132629},{"id":"https://openalex.org/C158154518","wikidata":"https://www.wikidata.org/wiki/Q7310970","display_name":"Relevance (law)","level":2,"score":0.45989999175071716},{"id":"https://openalex.org/C55105296","wikidata":"https://www.wikidata.org/wiki/Q841382","display_name":"Interaction network","level":3,"score":0.41190001368522644},{"id":"https://openalex.org/C53811970","wikidata":"https://www.wikidata.org/wiki/Q5062194","display_name":"Centrality","level":2,"score":0.4081999957561493},{"id":"https://openalex.org/C519536355","wikidata":"https://www.wikidata.org/wiki/Q21021151","display_name":"Repurposing","level":2,"score":0.3935000002384186},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3869999945163727},{"id":"https://openalex.org/C116834253","wikidata":"https://www.wikidata.org/wiki/Q2039217","display_name":"Identification (biology)","level":2,"score":0.3864000141620636},{"id":"https://openalex.org/C78458016","wikidata":"https://www.wikidata.org/wiki/Q840400","display_name":"Evolutionary biology","level":1,"score":0.38519999384880066},{"id":"https://openalex.org/C2777212361","wikidata":"https://www.wikidata.org/wiki/Q5127848","display_name":"Class (philosophy)","level":2,"score":0.3547999858856201},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.3398999869823456},{"id":"https://openalex.org/C153991713","wikidata":"https://www.wikidata.org/wiki/Q17142856","display_name":"Niche","level":2,"score":0.33959999680519104},{"id":"https://openalex.org/C188880781","wikidata":"https://www.wikidata.org/wiki/Q2430501","display_name":"Three-domain system","level":4,"score":0.3212999999523163},{"id":"https://openalex.org/C11804247","wikidata":"https://www.wikidata.org/wiki/Q896177","display_name":"Protein\u2013protein interaction","level":2,"score":0.31439998745918274},{"id":"https://openalex.org/C47701112","wikidata":"https://www.wikidata.org/wiki/Q735188","display_name":"Protein structure","level":2,"score":0.30979999899864197},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.30000001192092896},{"id":"https://openalex.org/C32946077","wikidata":"https://www.wikidata.org/wiki/Q618079","display_name":"Network analysis","level":2,"score":0.2985000014305115},{"id":"https://openalex.org/C103637391","wikidata":"https://www.wikidata.org/wiki/Q5308921","display_name":"Drug repositioning","level":3,"score":0.29089999198913574},{"id":"https://openalex.org/C2780217385","wikidata":"https://www.wikidata.org/wiki/Q2389284","display_name":"Hierarchical organization","level":2,"score":0.290800005197525},{"id":"https://openalex.org/C10010492","wikidata":"https://www.wikidata.org/wiki/Q3142557","display_name":"Protein sequencing","level":4,"score":0.2888000011444092},{"id":"https://openalex.org/C2778112365","wikidata":"https://www.wikidata.org/wiki/Q3511065","display_name":"Sequence (biology)","level":2,"score":0.2865999937057495},{"id":"https://openalex.org/C144292202","wikidata":"https://www.wikidata.org/wiki/Q898273","display_name":"Protein domain","level":3,"score":0.28459998965263367},{"id":"https://openalex.org/C171897839","wikidata":"https://www.wikidata.org/wiki/Q417841","display_name":"Protein family","level":3,"score":0.2824999988079071},{"id":"https://openalex.org/C180916674","wikidata":"https://www.wikidata.org/wiki/Q3711935","display_name":"Diversification (marketing strategy)","level":2,"score":0.2606000006198883},{"id":"https://openalex.org/C12426560","wikidata":"https://www.wikidata.org/wiki/Q189569","display_name":"Basis (linear algebra)","level":2,"score":0.25949999690055847},{"id":"https://openalex.org/C45484198","wikidata":"https://www.wikidata.org/wiki/Q827246","display_name":"Sequence alignment","level":4,"score":0.25099998712539673}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.10.17.759831","doi":"https://doi.org/10.64898/2026.10.17.759831","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.17.759831","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/19/2026.10.17.759831.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.10.17.759831","doi":"https://doi.org/10.64898/2026.10.17.759831","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.17.759831","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/19/2026.10.17.759831.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G2560678733","display_name":null,"funder_award_id":"20020220100181BA","funder_id":"https://openalex.org/F4320323257","funder_display_name":"Universidad de Buenos Aires"},{"id":"https://openalex.org/G8518400251","display_name":null,"funder_award_id":"20020220100181BA","funder_id":"https://openalex.org/F4320335478","funder_display_name":"Secretar\u00eda de Ciencia y T\u00e9cnica, Universidad de Buenos Aires"}],"funders":[{"id":"https://openalex.org/F4320321594","display_name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","ror":"https://ror.org/03cqe8w59"},{"id":"https://openalex.org/F4320323257","display_name":"Universidad de Buenos Aires","ror":"https://ror.org/0081fs513"},{"id":"https://openalex.org/F4320335478","display_name":"Secretar\u00eda de Ciencia y T\u00e9cnica, Universidad de Buenos Aires","ror":null}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7222950704.pdf","grobid_xml":"https://content.openalex.org/works/W7222950704.grobid-xml"},"referenced_works_count":2,"referenced_works":["https://openalex.org/W4306742781","https://openalex.org/W4409260296"],"related_works":["https://openalex.org/W2755928239","https://openalex.org/W2075835708","https://openalex.org/W2013987468","https://openalex.org/W1986199568","https://openalex.org/W2465602005","https://openalex.org/W3112417038","https://openalex.org/W2103935383","https://openalex.org/W7134849686","https://openalex.org/W7162433276","https://openalex.org/W2033915366"],"abstract_inverted_index":{"Abstract":[0],"Studying":[1],"protein":[2,19,86,161,174],"binding":[3,41,117],"sites":[4,42,132],"helps":[5],"explain":[6],"ligand":[7,187],"recognition":[8,30,97,145],"and":[9,14,49,119,139,163,176,183,190],"selectivity,":[10,189],"informing":[11],"drug":[12,106],"development":[13],"repurposing.":[15],"Here,":[16],"we":[17,108],"combine":[18],"language":[20],"model":[21],"embeddings":[22,45],"with":[23,59,88,135],"network":[24,68,72,155],"analysis":[25],"to":[26,95],"investigate":[27],"how":[28,154],"local":[29,60,164],"environments":[31],"organize":[32],"across":[33,147,166],"scales.":[34],"We":[35],"represented":[36],"121,673":[37],"non-redundant,":[38],"experimentally":[39],"identified":[40],"using":[43],"ProtT5":[44],"of":[46,67,105,186],"ligand-contacting":[47],"residues":[48],"constructed":[50],"a":[51,102,178],"mutual":[52],"nearest-neighbor":[53],"network.":[54],"Embedding":[55],"proximity":[56],"was":[57],"associated":[58],"structural":[61,65,126,182],"similarity,":[62],"supporting":[63],"the":[64,71,77],"relevance":[66],"relationships.":[69],"Globally,":[70],"exhibited":[73],"ligand-related":[74],"organization.":[75],"At":[76],"mesoscopic":[78],"scale,":[79],"communities":[80,111],"revealed":[81],"heterogeneous":[82],"landscapes":[83],"within":[84,112,124,160],"established":[85],"classifications,":[87],"InterPro":[89,141],"categories":[90,162],"ranging":[91],"from":[92],"compact":[93],"neighborhoods":[94],"dispersed":[96],"environments.":[98],"Focusing":[99],"on":[100],"kinases,":[101],"major":[103],"class":[104],"targets,":[107],"found":[109],"that":[110],"individual":[113],"proteins":[114,134],"distinguished":[115],"separate":[116],"regions":[118],"resolved":[120],"recurrent":[121],"residue-defined":[122],"microenvironments":[123],"broad":[125],"classes.":[127],"Local":[128],"similarities":[129,165],"also":[130],"connected":[131],"in":[133],"low":[136],"sequence":[137],"identity":[138],"non-overlapping":[140],"annotations,":[142],"suggesting":[143],"shared":[144],"features":[146],"distant":[148],"proteins.":[149],"Together,":[150],"these":[151],"results":[152],"show":[153],"organization":[156],"captures":[157],"both":[158],"diversification":[159],"their":[167],"boundaries.":[168],"This":[169],"multiscale":[170],"framework":[171],"complements":[172],"conventional":[173],"classifications":[175],"provides":[177],"basis":[179],"for":[180],"prioritizing":[181],"biochemical":[184],"investigations":[185],"cross-reactivity,":[188],"repurposing":[191],"opportunities.":[192]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2026-10-20T00:00:00"}