{"id":"https://openalex.org/W7225323816","doi":"https://doi.org/10.64898/2026.11.04.764416","title":"Harnessing catalytic knowledge to guide enzyme discovery and evolution with AlphaEnzyme","display_name":"Harnessing catalytic knowledge to guide enzyme discovery and evolution with AlphaEnzyme","publication_year":2026,"publication_date":"2026-11-05","ids":{"openalex":"https://openalex.org/W7225323816","doi":"https://doi.org/10.64898/2026.11.04.764416"},"language":"en","primary_location":{"id":"doi:10.64898/2026.11.04.764416","doi":"https://doi.org/10.64898/2026.11.04.764416","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.04.764416","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/05/2026.11.04.764416.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-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/05/2026.11.04.764416.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5160860286","display_name":"Yong Liu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I183067930","display_name":"Shanghai Jiao Tong University","ror":"https://ror.org/0220qvk04","country_code":"CN","type":"education","lineage":["https://openalex.org/I183067930"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Yong Liu","raw_affiliation_strings":["Shanghai Jiao Tong University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Shanghai Jiao Tong University","institution_ids":["https://openalex.org/I183067930"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5075817762","display_name":"Shuangjia Zheng","orcid":"https://orcid.org/0000-0001-9747-4285","observed_orcids":["https://orcid.org/0000-0001-9747-4285"]},"institutions":[{"id":"https://openalex.org/I183067930","display_name":"Shanghai Jiao Tong University","ror":"https://ror.org/0220qvk04","country_code":"CN","type":"education","lineage":["https://openalex.org/I183067930"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Shuangjia Zheng","raw_affiliation_strings":["Shanghai Jiao Tong University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Shanghai Jiao Tong University","institution_ids":["https://openalex.org/I183067930"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5075817762"],"corresponding_institution_ids":["https://openalex.org/I183067930"],"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/T10404","display_name":"Enzyme Catalysis and Immobilization","score":0.9330999851226807,"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/T10404","display_name":"Enzyme Catalysis and Immobilization","score":0.9330999851226807,"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/T10044","display_name":"Protein Structure and Dynamics","score":0.0414000004529953,"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":0.007899999618530273,"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/enzyme-discovery","display_name":"enzyme discovery","score":0.6949999928474426},{"id":"https://openalex.org/keywords/enzyme-evolution","display_name":"enzyme evolution","score":0.8849999904632568},{"id":"https://openalex.org/keywords/trpb","display_name":"trpB","score":0.7630000114440918},{"id":"https://openalex.org/keywords/enzyme-kinetics","display_name":"enzyme kinetics","score":0.4560000002384186}],"concepts":[{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.625},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.5550000071525574},{"id":"https://openalex.org/C2779343474","wikidata":"https://www.wikidata.org/wiki/Q3109175","display_name":"Context (archaeology)","level":2,"score":0.527999997138977},{"id":"https://openalex.org/C2776359362","wikidata":"https://www.wikidata.org/wiki/Q2145286","display_name":"Representation (politics)","level":3,"score":0.4921000003814697},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.47519999742507935},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.46000000834465027},{"id":"https://openalex.org/C183696295","wikidata":"https://www.wikidata.org/wiki/Q2487696","display_name":"Biochemical engineering","level":1,"score":0.4133000075817108},{"id":"https://openalex.org/C2776877979","wikidata":"https://www.wikidata.org/wiki/Q424288","display_name":"Transaminase","level":3,"score":0.4025999903678894},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.3822999894618988},{"id":"https://openalex.org/C124101348","wikidata":"https://www.wikidata.org/wiki/Q172491","display_name":"Data mining","level":1,"score":0.3352000117301941},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3278999924659729},{"id":"https://openalex.org/C64915919","wikidata":"https://www.wikidata.org/wiki/Q613955","display_name":"Michaelis\u2013Menten kinetics","level":4,"score":0.3276999890804291},{"id":"https://openalex.org/C147816474","wikidata":"https://www.wikidata.org/wiki/Q169525","display_name":"Protein engineering","level":3,"score":0.3215000033378601},{"id":"https://openalex.org/C9418097","wikidata":"https://www.wikidata.org/wiki/Q440681","display_name":"Directed evolution","level":4,"score":0.31949999928474426},{"id":"https://openalex.org/C90673727","wikidata":"https://www.wikidata.org/wiki/Q901718","display_name":"Product (mathematics)","level":2,"score":0.31209999322891235},{"id":"https://openalex.org/C55037315","wikidata":"https://www.wikidata.org/wiki/Q5421151","display_name":"Experimental data","level":2,"score":0.29820001125335693},{"id":"https://openalex.org/C4554734","wikidata":"https://www.wikidata.org/wiki/Q593744","display_name":"Knowledge base","level":2,"score":0.2973000109195709},{"id":"https://openalex.org/C186060115","wikidata":"https://www.wikidata.org/wiki/Q30336093","display_name":"Biological system","level":1,"score":0.29649999737739563},{"id":"https://openalex.org/C164226766","wikidata":"https://www.wikidata.org/wiki/Q7293202","display_name":"Rank (graph theory)","level":2,"score":0.29589998722076416},{"id":"https://openalex.org/C2778112365","wikidata":"https://www.wikidata.org/wiki/Q3511065","display_name":"Sequence (biology)","level":2,"score":0.2944999933242798},{"id":"https://openalex.org/C189430467","wikidata":"https://www.wikidata.org/wiki/Q7293293","display_name":"Ranking (information retrieval)","level":2,"score":0.2847999930381775},{"id":"https://openalex.org/C12426560","wikidata":"https://www.wikidata.org/wiki/Q189569","display_name":"Basis (linear algebra)","level":2,"score":0.2791000008583069},{"id":"https://openalex.org/C2777027219","wikidata":"https://www.wikidata.org/wiki/Q1284190","display_name":"Constant (computer programming)","level":2,"score":0.27900001406669617},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.26919999718666077},{"id":"https://openalex.org/C33923547","wikidata":"https://www.wikidata.org/wiki/Q395","display_name":"Mathematics","level":0,"score":0.2603999972343445},{"id":"https://openalex.org/C119857082","wikidata":"https://www.wikidata.org/wiki/Q2539","display_name":"Machine learning","level":1,"score":0.2538999915122986},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.25209999084472656}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.11.04.764416","doi":"https://doi.org/10.64898/2026.11.04.764416","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.04.764416","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/05/2026.11.04.764416.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-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.11.04.764416","doi":"https://doi.org/10.64898/2026.11.04.764416","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.04.764416","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/05/2026.11.04.764416.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-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G1333001686","display_name":null,"funder_award_id":"(24510714300","funder_id":"https://openalex.org/F4320321885","funder_display_name":"Science and Technology Commission of Shanghai Municipality"},{"id":"https://openalex.org/G4855278923","display_name":null,"funder_award_id":"2060302","funder_id":"https://openalex.org/F4320335787","funder_display_name":"Fundamental Research Funds for the Central Universities"},{"id":"https://openalex.org/G5153873114","display_name":null,"funder_award_id":"24ZR1440600","funder_id":"https://openalex.org/F4320309612","funder_display_name":"Natural Science Foundation of Shanghai"},{"id":"https://openalex.org/G6278460507","display_name":null,"funder_award_id":"2060302","funder_id":"https://openalex.org/F4320309612","funder_display_name":"Natural Science Foundation of Shanghai"},{"id":"https://openalex.org/G6687328163","display_name":null,"funder_award_id":"2060302","funder_id":"https://openalex.org/F4320321885","funder_display_name":"Science and Technology Commission of Shanghai Municipality"},{"id":"https://openalex.org/G7142395142","display_name":null,"funder_award_id":"62041209","funder_id":"https://openalex.org/F4320321001","funder_display_name":"National Natural Science Foundation of China"}],"funders":[{"id":"https://openalex.org/F4320309612","display_name":"Natural Science Foundation of Shanghai","ror":null},{"id":"https://openalex.org/F4320321001","display_name":"National Natural Science Foundation of China","ror":"https://ror.org/01h0zpd94"},{"id":"https://openalex.org/F4320321885","display_name":"Science and Technology Commission of Shanghai Municipality","ror":"https://ror.org/03kt66j61"},{"id":"https://openalex.org/F4320322999","display_name":"Shanghai Jiao Tong University","ror":"https://ror.org/0220qvk04"},{"id":"https://openalex.org/F4320335787","display_name":"Fundamental Research Funds for the Central Universities","ror":null}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7225323816.pdf","grobid_xml":"https://content.openalex.org/works/W7225323816.grobid-xml"},"referenced_works_count":40,"referenced_works":["https://openalex.org/W1607443777","https://openalex.org/W1986056153","https://openalex.org/W2041571635","https://openalex.org/W2048161430","https://openalex.org/W2767044445","https://openalex.org/W2778939204","https://openalex.org/W2809493191","https://openalex.org/W2887981960","https://openalex.org/W2890223884","https://openalex.org/W2922508190","https://openalex.org/W2938803199","https://openalex.org/W2950954328","https://openalex.org/W2967474035","https://openalex.org/W3144239152","https://openalex.org/W3194729882","https://openalex.org/W3209435229","https://openalex.org/W3211718555","https://openalex.org/W4226145240","https://openalex.org/W4283032119","https://openalex.org/W4313291879","https://openalex.org/W4327550249","https://openalex.org/W4362471278","https://openalex.org/W4376601927","https://openalex.org/W4386861232","https://openalex.org/W4388936967","https://openalex.org/W4395048825","https://openalex.org/W4399998351","https://openalex.org/W4401071498","https://openalex.org/W4401526016","https://openalex.org/W4402297934","https://openalex.org/W4402632138","https://openalex.org/W4406425222","https://openalex.org/W4406440058","https://openalex.org/W4408595553","https://openalex.org/W4408601309","https://openalex.org/W4410811941","https://openalex.org/W4411299206","https://openalex.org/W4411463597","https://openalex.org/W4414938342","https://openalex.org/W7126209807"],"related_works":["https://openalex.org/W7143966326","https://openalex.org/W7211952328","https://openalex.org/W7128689850","https://openalex.org/W7169604215","https://openalex.org/W7168051616","https://openalex.org/W7222902191","https://openalex.org/W7162066491","https://openalex.org/W7164752294","https://openalex.org/W7221406312","https://openalex.org/W4417536607"],"abstract_inverted_index":{"Retrieving":[0],"an":[1,38,48],"enzyme":[2,39,49],"for":[3,11,82,100,164,172],"a":[4,8,44,67,72,120,144,151,160],"target":[5],"reaction":[6],"provides":[7,159],"starting":[9,166],"point":[10],"evolution,":[12],"but":[13],"predicting":[14],"how":[15],"to":[16],"improve":[17],"it":[18],"remains":[19],"difficult.":[20],"This":[21],"requires":[22],"connecting":[23],"evolutionary":[24],"information":[25],"with":[26,51,107,139],"the":[27,83,90,95,108,137,140],"structural":[28],"and":[29,59,168],"chemical":[30],"context":[31],"of":[32,47,78,122],"catalysis.":[33],"Here":[34],"we":[35],"present":[36],"AlphaEnzyme,":[37],"foundation":[40],"model":[41,113],"built":[42],"on":[43],"structure-grounded":[45],"representation":[46],"paired":[50],"its":[52],"reaction,":[53],"from":[54],"which":[55],"catalytic":[56],"compatibility,":[57],"kinetics":[58],"mutational":[60],"response":[61],"are":[62],"read":[63],"out":[64],"together.":[65],"On":[66],"time-separated":[68],"benchmark,":[69],"AlphaEnzyme":[70,158],"achieves":[71],"top-1":[73],"catalyst":[74],"retrieval":[75],"success":[76],"rate":[77],"30.1%,":[79],"against":[80],"17.2%":[81],"strongest":[84],"baseline.":[85],"Michaelis":[86],"constant":[87],"predictions":[88],"achieve":[89],"highest":[91],"rank":[92],"correlations":[93],"among":[94],"compared":[96],"methods,":[97],"reaching":[98],"0.64":[99],"enzymes":[101,167],"sharing":[102],"at":[103,119],"most":[104],"40%":[105],"identity":[106],"kinetic":[109],"training":[110],"set.":[111],"The":[112],"also":[114],"enriches":[115],"high-fitness":[116],"TrpB":[117],"variants":[118,135],"budget":[121],"16":[123],"candidates":[124],"without":[125],"target-specific":[126],"fitness":[127],"training.":[128],"In":[129],"prospective":[130],"transaminase":[131],"engineering,":[132],"several":[133],"prioritized":[134],"exceed":[136],"parent,":[138],"best":[141],"design":[142],"yielding":[143],"30.4-fold":[145],"increase":[146],"in":[147,150],"product":[148],"signal":[149],"lysate-based":[152],"assay":[153],"while":[154],"retaining":[155],"(R)-selectivity.":[156],"Together,":[157],"common":[161],"molecular":[162],"basis":[163],"selecting":[165],"prioritizing":[169],"sequence":[170],"changes":[171],"their":[173],"improvement.":[174]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-11-06T00:00:00"}