{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:28:52Z","timestamp":1772166532714,"version":"3.50.1"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Grant Agency of Masaryk University","award":["CZ.02.2.69\/0.0\/0.0\/19_073\/0016943"],"award-info":[{"award-number":["CZ.02.2.69\/0.0\/0.0\/19_073\/0016943"]}]},{"DOI":"10.13039\/501100017520","name":"Fakulta Informa\u010dn\u00edch Technologi\u00ed, Vysok\u00e9 U\u010den\u00ed Technick\u00e9 v Brn\u011b","doi-asserted-by":"publisher","award":["FIT-S-23-8209"],"award-info":[{"award-number":["FIT-S-23-8209"]}],"id":[{"id":"10.13039\/501100017520","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001823","name":"Ministerstvo \u0160kolstv\u00ed, Ml\u00e1de\u017ee a T\u011blov\u00fdchovy","doi-asserted-by":"publisher","award":["LM2023069"],"award-info":[{"award-number":["LM2023069"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","award":["857560"],"award-info":[{"award-number":["857560"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union - Next Generation EU","award":["LX22NPO5102"],"award-info":[{"award-number":["LX22NPO5102"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cheminform"],"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      The quest to predict and understand protein evolution has been hindered by limitations on both the theoretical and the experimental fronts. Most existing theoretical models of evolution are descriptive, rather than predictive, leaving the final modifications in the hands of researchers. Existing experimental techniques to help probe the evolutionary sequence space of proteins, such as directed evolution, are resource-intensive and require specialised skills. We present the successor sequence predictor (SSP) as an innovative solution. Successor sequence predictor is an in silico protein design method that mimics laboratory-based protein evolution by reconstructing a protein's evolutionary history and suggesting future amino acid substitutions based on trends observed in that history through carefully selected physicochemical descriptors. This approach enhances specialised proteins by predicting mutations that improve desired properties, such as thermostability, activity, and solubility. Successor Sequence Predictor can thus be used as a general protein engineering tool to develop practically useful proteins. The code of the Successor Sequence Predictor is provided\u00a0at\u00a0\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/github.com\/loschmidt\/successor-sequence-predictor\" ext-link-type=\"uri\">https:\/\/github.com\/loschmidt\/successor-sequence-predictor<\/jats:ext-link>\n                      , and the design of mutations will be also possible via an easy-to-use web server\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/loschmidt.chemi.muni.cz\/fireprotasr\/\" ext-link-type=\"uri\">https:\/\/loschmidt.chemi.muni.cz\/fireprotasr\/<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Scientific Contribution<\/jats:title>\n                    <jats:p>The Successor Sequence Predictor advances protein evolution prediction at the amino acid level by integrating ancestral sequence reconstruction with a novel in silico approach that models evolutionary trends through selected physicochemical descriptors. Unlike prior work, SSP can forecast future amino acid substitutions that enhance protein properties such as thermostability, activity, and solubility. This method reduces reliance on resource-intensive directed evolution techniques while providing a generalizable, predictive tool for protein engineering.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s13321-025-00971-z","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T12:00:26Z","timestamp":1742558426000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anticipating protein evolution with successor sequence predictor"],"prefix":"10.1186","volume":"17","author":[{"given":"Rayyan Tariq","family":"Khan","sequence":"first","affiliation":[]},{"given":"Pavel","family":"Kohout","sequence":"additional","affiliation":[]},{"given":"Milos","family":"Musil","sequence":"additional","affiliation":[]},{"given":"Monika","family":"Rosinska","sequence":"additional","affiliation":[]},{"given":"Jiri","family":"Damborsky","sequence":"additional","affiliation":[]},{"given":"Stanislav","family":"Mazurenko","sequence":"additional","affiliation":[]},{"given":"David","family":"Bednar","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"971_CR1","unstructured":"Hall BK, Hallgrimsson B (2014) Strickberger\u2019s evolution. Jones And Bartlett."},{"key":"971_CR2","volume-title":"The causes of molecular evolution","author":"JH Gillespie","year":"1994","unstructured":"Gillespie JH (1994) The causes of molecular evolution. Oxford University Press"},{"key":"971_CR3","volume-title":"The neutral theory of molecular evolution","author":"M Kimura","year":"1985","unstructured":"Kimura M (1985) The neutral theory of molecular evolution. Cambridge University Press"},{"key":"971_CR4","doi-asserted-by":"publisher","unstructured":"Nosil P, Flaxman SM, Feder JL, Gompert Z (2020) Increasing our ability to predict contemporary evolution. Nat Commun 11(1) https:\/\/doi.org\/10.1038\/s41467-020-19437-x","DOI":"10.1038\/s41467-020-19437-x"},{"issue":"8","key":"971_CR5","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1038\/nrg2146","volume":"8","author":"A Eyre-Walker","year":"2007","unstructured":"Eyre-Walker A, Keightley PD (2007) The distribution of fitness effects of new mutations. Nat Rev Genet 8(8):610\u2013618. https:\/\/doi.org\/10.1038\/nrg2146","journal-title":"Nat Rev Genet"},{"issue":"5","key":"971_CR6","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nrg1838","volume":"7","author":"C P\u00e1l","year":"2006","unstructured":"P\u00e1l C, Papp B, Lercher MJ (2006) An integrated view of protein evolution. Nat Rev Genet 7(5):337\u2013348. https:\/\/doi.org\/10.1038\/nrg1838","journal-title":"Nat Rev Genet"},{"issue":"1877","key":"971_CR7","doi-asserted-by":"publisher","first-page":"20220055","DOI":"10.1098\/rstb.2022.0055","volume":"378","author":"AV Cano","year":"2023","unstructured":"Cano AV, Gitschlag BL, Rozho\u0148ov\u00e1 H, Stoltzfus A, McCandlish DM, Payne JL (2023) Mutation bias and the predictability of evolution. Philos Trans R Soc B 378(1877):20220055. https:\/\/doi.org\/10.1098\/rstb.2022.0055","journal-title":"Philos Trans R Soc B"},{"key":"971_CR8","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1038\/s41592-019-0496-6","volume":"16","author":"KK Yang","year":"2019","unstructured":"Yang KK, Wu Z, Arnold FH (2019) Machine-learning-guided directed evolution for protein engineering. Nat Methods 16:687\u2013694. https:\/\/doi.org\/10.1038\/s41592-019-0496-6","journal-title":"Nat Methods"},{"issue":"41","key":"971_CR9","doi-asserted-by":"publisher","first-page":"14420","DOI":"10.1002\/anie.201907729","volume":"58","author":"FH Arnold","year":"2019","unstructured":"Arnold FH (2019) Innovation by evolution: bringing new chemistry to life (nobel lecture). Angew Chem 58(41):14420\u201314426. https:\/\/doi.org\/10.1002\/anie.201907729","journal-title":"Angew Chem"},{"issue":"3","key":"971_CR10","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1093\/genetics\/155.3.1405","volume":"155","author":"JC Fay","year":"2000","unstructured":"Fay JC, Wu CI (2000) Hitchhiking under positive Darwinian selection. Genetics 155(3):1405\u20131413. https:\/\/doi.org\/10.1093\/genetics\/155.3.1405","journal-title":"Genetics"},{"issue":"4","key":"971_CR11","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1038\/s41589-022-00967-y","volume":"18","author":"SA Raven","year":"2022","unstructured":"Raven SA, Payne B, Mitchell AF, Rackham O (2022) In silico evolution of nucleic acid-binding proteins from a nonfunctional scaffold. Nat Chem Biol 18(4):403\u2013411. https:\/\/doi.org\/10.1038\/s41589-022-00967-y","journal-title":"Nat Chem Biol"},{"issue":"1","key":"971_CR12","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1093\/nar\/28.1.374","volume":"28","author":"S Kawashima","year":"2000","unstructured":"Kawashima S (2000) AAindex: amino acid index database. Nucleic Acids Res 28(1):374\u2013374. https:\/\/doi.org\/10.1093\/nar\/28.1.374","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"971_CR13","doi-asserted-by":"publisher","first-page":"2576","DOI":"10.1021\/acscatal.2c03859","volume":"13","author":"J Livada","year":"2023","unstructured":"Livada J, Vargas AM, Martinez CA, Lewis RD (2023) Ancestral sequence reconstruction enhances gene mining efforts for industrial ene reductases by expanding enzyme panels with thermostable catalysts. ACS Catal 13(4):2576\u20132585. https:\/\/doi.org\/10.1021\/acscatal.2c03859","journal-title":"ACS Catal"},{"key":"971_CR14","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbaa337","author":"M Musil","year":"2020","unstructured":"Musil M, Khan RT, Beier A, Stourac J, Konegger H, Damborsky J, Bednar D (2020) FireProtASR: a web server for fully automated ancestral sequence reconstruction. Brief Bioinform. https:\/\/doi.org\/10.1093\/bib\/bbaa337","journal-title":"Brief Bioinform"},{"issue":"12","key":"971_CR15","doi-asserted-by":"publisher","first-page":"4571","DOI":"10.1021\/jacsau.4c00653","volume":"4","author":"K Prakinee","year":"2024","unstructured":"Prakinee K, Phaisan S, Kongjaroon S, Chaiyen P (2024) Ancestral sequence reconstruction for designing biocatalysts and investigating their functional mechanisms. JACS Au 4(12):4571\u20134591. https:\/\/doi.org\/10.1021\/jacsau.4c00653","journal-title":"JACS Au"},{"issue":"2","key":"971_CR16","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1002\/cctc.201801644","volume":"11","author":"Y Gumulya","year":"2019","unstructured":"Gumulya Y, Huang W, D\u2019Cunha SA, Richards KE, Thomson RE, Hunter DJ, Baek JM, Harris KL, Boden M, De Voss JJ, Hayes MA (2019) Engineering thermostable CYP2D enzymes for biocatalysis using combinatorial libraries of ancestors for directed evolution (CLADE). ChemCatChem 11(2):841\u2013850. https:\/\/doi.org\/10.1002\/cctc.201801644","journal-title":"ChemCatChem"},{"issue":"11","key":"971_CR17","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1038\/s41929-018-0159-5","volume":"1","author":"Y Gumulya","year":"2018","unstructured":"Gumulya Y, Baek JM, Wun SJ, Thomson RE, Harris KL, Hunter DJ, Behrendorff JB, Kulig J, Zheng S, Wu X, Wu B (2018) Engineering highly functional thermostable proteins using ancestral sequence reconstruction. Nat Catal 1(11):878\u2013888. https:\/\/doi.org\/10.1038\/s41929-018-0159-5","journal-title":"Nat Catal"},{"issue":"23","key":"971_CR18","doi-asserted-by":"publisher","first-page":"17893","DOI":"10.1021\/acscatal.4c03738","volume":"14","author":"CK Brennan","year":"2024","unstructured":"Brennan CK, Livada J, Martinez CA, Lewis RD (2024) Ancestral sequence reconstruction meets machine learning: ene reductase thermostabilization yields enzymes with improved reactivity profiles. ACS Catal 14(23):17893\u201317900. https:\/\/doi.org\/10.1021\/acscatal.4c03738","journal-title":"ACS Catal"},{"issue":"11","key":"971_CR19","doi-asserted-by":"publisher","first-page":"5977","DOI":"10.1073\/pnas.1916786117","volume":"117","author":"G Slodkowicz","year":"2020","unstructured":"Slodkowicz G, Goldman N (2020) Integrated structural and evolutionary analysis reveals common mechanisms underlying adaptive evolution in mammals. Proc Natl Acad Sci 117(11):5977\u20135986. https:\/\/doi.org\/10.1073\/pnas.1916786117","journal-title":"Proc Natl Acad Sci"},{"key":"971_CR20","doi-asserted-by":"publisher","DOI":"10.1201\/9781351072427\/handbook-biochemistry-gerald-fasman","volume-title":"Practical handbook of biochemistry and molecular biology","author":"GD Fasman","year":"1989","unstructured":"Fasman GD (1989) Practical handbook of biochemistry and molecular biology. CRC Press, New York. https:\/\/doi.org\/10.1201\/9781351072427\/handbook-biochemistry-gerald-fasman"},{"issue":"3","key":"971_CR21","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/0022-5193(73)90075-1","volume":"39","author":"DE Goldsack","year":"1973","unstructured":"Goldsack DE, Chalifoux RC (1973) Contribution of the free energy of mixing of hydrophobic side chains to the stability of the tertiary structure of proteins. J Theor Biol 39(3):645\u2013651. https:\/\/doi.org\/10.1016\/0022-5193(73)90075-1","journal-title":"J Theor Biol"},{"issue":"4418","key":"971_CR22","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1126\/science.493962","volume":"206","author":"RV Wolfenden","year":"1979","unstructured":"Wolfenden RV, Cullis PM, Southgate CCF (1979) Water, protein folding, and the genetic code. Science 206(4418):575\u2013577. https:\/\/doi.org\/10.1126\/science.493962","journal-title":"Science"},{"issue":"4","key":"971_CR23","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1111\/j.1399-3011.1988.tb01258.x","volume":"32","author":"R Bhaskran","year":"1988","unstructured":"Bhaskran R, Ponnuswamy PK (1988) Positional flexibilities of amino acid residues in globular proteins. Int J Pept Protein Res 32(4):241\u2013255. https:\/\/doi.org\/10.1111\/j.1399-3011.1988.tb01258.x","journal-title":"Int J Pept Protein Res"},{"issue":"2","key":"971_CR24","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1016\/0003-9861(74)90352-x","volume":"161","author":"HB Bull","year":"1974","unstructured":"Bull HB, Breese K (1974) Surface tension of amino acid solutions: a hydrophobicity scale of the amino acid residues. Arch Biochem Biophys 161(2):665\u2013670. https:\/\/doi.org\/10.1016\/0003-9861(74)90352-x","journal-title":"Arch Biochem Biophys"},{"issue":"4","key":"971_CR25","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1111\/j.1399-3011.1988.tb01261.x","volume":"32","author":"J-L Fauchere","year":"2009","unstructured":"Fauchere J-L, Charton M, Kier LB, Verloop A, Pliska V (2009) Amino acid side chain parameters for correlation studies in biology and pharmacology. Int J Pept Protein Res 32(4):269\u2013278. https:\/\/doi.org\/10.1111\/j.1399-3011.1988.tb01261.x","journal-title":"Int J Pept Protein Res"},{"issue":"2","key":"971_CR26","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/0022-5193(68)90069-6","volume":"21","author":"JM Zimmerman","year":"1968","unstructured":"Zimmerman JM, Eliezer N, Simha R (1968) The characterization of amino acid sequences in proteins by statistical methods. J Theor Biol 21(2):170\u2013201. https:\/\/doi.org\/10.1016\/0022-5193(68)90069-6","journal-title":"J Theor Biol"},{"issue":"1","key":"971_CR27","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1093\/nar\/gkn201","volume":"36","author":"M Johnson","year":"2008","unstructured":"Johnson M, Zaretskaya I, Raytselis Y, Merezhuk Y, McGinnis S, Madden TL (2008) NCBI BLAST: a better web interface. Nucleic Acids Res 36(1):5\u20139. https:\/\/doi.org\/10.1093\/nar\/gkn201","journal-title":"Nucleic Acids Res"},{"issue":"483","key":"971_CR28","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1198\/016214508000000454","volume":"103","author":"Y Liu","year":"2008","unstructured":"Liu Y, Hayes DN, Nobel A, Marron JS (2008) Statistical significance of clustering for high-dimension, low-sample size data. J Am Stat Assoc 103(483):1281\u20131293","journal-title":"J Am Stat Assoc"},{"key":"971_CR29","doi-asserted-by":"publisher","unstructured":"Sievers F, Higgins DG (2014) Clustal omega. Curr Protoc Bioinformat. 48(1) https:\/\/doi.org\/10.1002\/0471250953.bi0313s48","DOI":"10.1002\/0471250953.bi0313s48"},{"issue":"9","key":"971_CR30","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1093\/bioinformatics\/btu033","volume":"30","author":"A Stamatakis","year":"2014","unstructured":"Stamatakis A (2014) RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics 30(9):1312\u20131313. https:\/\/doi.org\/10.1093\/bioinformatics\/btu033","journal-title":"Bioinformatics"},{"key":"971_CR31","doi-asserted-by":"publisher","first-page":"0193","DOI":"10.1038\/s41559-017-0193","volume":"1","author":"F Tria","year":"2017","unstructured":"Tria F, Landan G, Dagan T (2017) Phylogenetic rooting using minimal ancestor deviation. Nat Ecol Evol 1:0193. https:\/\/doi.org\/10.1038\/s41559-017-0193","journal-title":"Nat Ecol Evol"},{"issue":"9","key":"971_CR32","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.1093\/molbev\/msq081","volume":"27","author":"V Hanson-Smith","year":"2010","unstructured":"Hanson-Smith V, Kolaczkowski B, Thornton JW (2010) Robustness of ancestral sequence reconstruction to phylogenetic uncertainty. Mol Biol Evol 27(9):1988\u20131999. https:\/\/doi.org\/10.1093\/molbev\/msq081","journal-title":"Mol Biol Evol"},{"key":"971_CR33","unstructured":"sklearn.linear_model.LinearRegression (2023) Scikit-Learn. https:\/\/scikit-learn.org\/stable\/modules\/generated\/sklearn.linear_model.LinearRegression.html"},{"issue":"9","key":"971_CR34","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.1073\/pnas.1614437114","volume":"114","author":"JR Klesmith","year":"2017","unstructured":"Klesmith JR, Bacik J-P, Wrenbeck EE, Michalczyk R, Whitehead TA (2017) Trade-offs between enzyme fitness and solubility illuminated by deep mutational scanning. Proc Natl Acad Sci 114(9):2265\u20132270. https:\/\/doi.org\/10.1073\/pnas.1614437114","journal-title":"Proc Natl Acad Sci"},{"issue":"3","key":"971_CR35","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1016\/j.jmb.2006.11.061","volume":"366","author":"AV Gribenko","year":"2007","unstructured":"Gribenko AV, Makhatadze GI (2007) Role of the charge-charge interactions in defining stability and halophilicity of the CspB proteins. J Mol Biol 366(3):842\u2013856. https:\/\/doi.org\/10.1016\/j.jmb.2006.11.061","journal-title":"J Mol Biol"},{"issue":"14","key":"971_CR36","doi-asserted-by":"publisher","first-page":"e112","DOI":"10.1093\/nar\/gku511","volume":"42","author":"A Melnikov","year":"2014","unstructured":"Melnikov A, Rogov P, Wang L, Gnirke A, Mikkelsen TS (2014) Comprehensive mutational scanning of a kinase in vivo reveals substrate-dependent fitness landscapes. Nucleic Acids Res 42(14):e112\u2013e112. https:\/\/doi.org\/10.1093\/nar\/gku511","journal-title":"Nucleic Acids Res"},{"key":"971_CR37","doi-asserted-by":"publisher","first-page":"6339","DOI":"10.1016\/j.csbj.2022.11.009","volume":"20","author":"J Veleck\u00fd","year":"2022","unstructured":"Veleck\u00fd J, Hamsikova M, Stourac J, Musil M, Damborsky J, Bednar D, Mazurenko S (2022) SoluProtMutDB: a manually curated database of protein solubility changes upon mutations. Comput Struct Biotechnol J 20:6339\u20136347. https:\/\/doi.org\/10.1016\/j.csbj.2022.11.009","journal-title":"Comput Struct Biotechnol J"},{"issue":"D1","key":"971_CR38","doi-asserted-by":"publisher","first-page":"D319","DOI":"10.1093\/nar\/gkaa981","volume":"49","author":"J Stourac","year":"2020","unstructured":"Stourac J, Dubrava J, Musil M, Horackova J, Damborsky J, Mazurenko S, Bednar D (2020) FireProtDB: database of manually curated protein stability data. Nucleic Acids Res 49(D1):D319\u2013D324. https:\/\/doi.org\/10.1093\/nar\/gkaa981","journal-title":"Nucleic Acids Res"},{"key":"971_CR39","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.sbi.2021.04.001","volume":"69","author":"MA Spence","year":"2021","unstructured":"Spence MA, Kaczmarski JA, Saunders JW, Jackson CJ (2021) Ancestral sequence reconstruction for protein engineers. Curr Opin Struct Biol 69:131\u2013141. https:\/\/doi.org\/10.1016\/j.sbi.2021.04.001","journal-title":"Curr Opin Struct Biol"},{"key":"971_CR40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2148-4-33","volume":"4","author":"W Cai","year":"2004","unstructured":"Cai W, Pei J, Grishin NV (2004) Reconstruction of ancestral protein sequences and its applications. BMC Evol Biol 4:1\u201323. https:\/\/doi.org\/10.1186\/1471-2148-4-33","journal-title":"BMC Evol Biol"},{"issue":"14","key":"971_CR41","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1002\/cbic.201700197","volume":"18","author":"P Babkova","year":"2017","unstructured":"Babkova P, Sebestova E, Brezovsky J, Chaloupkova R, Damborsky J (2017) Ancestral haloalkane dehalogenases show robustness and unique substrate specificity. ChemBioChem 18(14):1448\u20131456. https:\/\/doi.org\/10.1002\/cbic.201700197","journal-title":"ChemBioChem"},{"key":"971_CR42","doi-asserted-by":"publisher","unstructured":"Risso VA, Sanchez-Ruiz JM (2017) Resurrected ancestral proteins as scaffolds for protein engineering. In: Directed enzyme evolution: advances and applications. pp. 229\u2013255. https:\/\/doi.org\/10.1007\/978-3-319-50413-1_9","DOI":"10.1007\/978-3-319-50413-1_9"},{"issue":"10","key":"971_CR43","doi-asserted-by":"publisher","first-page":"102435","DOI":"10.1016\/j.jbc.2022.102435","volume":"298","author":"RE Thomson","year":"2022","unstructured":"Thomson RE, Carrera-Pacheco SE, Gillam EM (2022) Engineering functional thermostable proteins using ancestral sequence reconstruction. J Biol Chem 298(10):102435. https:\/\/doi.org\/10.1016\/j.jbc.2022.102435","journal-title":"J Biol Chem"},{"key":"971_CR44","doi-asserted-by":"publisher","unstructured":"Kohout P, Vasina M, Majerova M, Novakova V, Damborsky J, Bednar D, Marek M, Prokop Z, Mazurenko S (2025). Engineering Dehalogenase Enzymes Using Variational Autoencoder-Generated Latent Spaces and Microfluidics. JACS Au.\u00a0https:\/\/doi.org\/10.1021\/jacsau.4c01101.","DOI":"10.1021\/jacsau.4c01101"}],"container-title":["Journal of Cheminformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13321-025-00971-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13321-025-00971-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13321-025-00971-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T12:00:35Z","timestamp":1742558435000},"score":1,"resource":{"primary":{"URL":"https:\/\/jcheminf.biomedcentral.com\/articles\/10.1186\/s13321-025-00971-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,21]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["971"],"URL":"https:\/\/doi.org\/10.1186\/s13321-025-00971-z","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.06.08.598054","asserted-by":"object"}]},"ISSN":["1758-2946"],"issn-type":[{"value":"1758-2946","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,21]]},"assertion":[{"value":"18 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"34"}}