{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T15:18:08Z","timestamp":1783005488039,"version":"3.54.5"},"reference-count":57,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Postharvest losses in climacteric fruits are largely driven by ethylene, and inhibiting its biosynthesis is an active research goal. RNA aptamers are attractive candidates for modulating the two rate-limiting enzymes\u2014ACC oxidase (ACO) and ACC synthase (ACS), without the toxicity concerns of chemical inhibitors. We built a computational pipeline using three independent docking engines: ITD DOCK (Graphics Processing Unit [GPU]-accelerated, Assisted Model Building with Energy Refinement [AMBER] force fields), HDOCK Lite (knowledge-based geometric potentials), and HADDOCK3 (semi-flexible refinement), screened against large aptamer libraries. Applied to ACC oxidase with 9813 aptamers, engine scores were largely complementary, with all pairwise correlations statistically non-significant on the full dataset (Spearman |\u03c1|\u22640.013, p&gt;0.20 for all pairs, n=9813). A Random Forest on sequence-only features failed to predict docking scores (R2=\u22120.012, Root Mean Square Error [RMSE] = 21.79 kcal\/mol), while a positive-control model on HADDOCK3 energy components achieved R2=0.991, confirming that predictive information only becomes available after docking. A preliminary pilot screening against ACC synthase (n=97 valid complexes) suggested pipeline generalizability to a second structurally distinct target and identified two putative dual-active candidates, pending confirmation against the full library. The complete workflow is automated in AptaDock, a standalone desktop application.<\/jats:p>","DOI":"10.3390\/ijms27135947","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T14:51:25Z","timestamp":1783003885000},"page":"5947","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Multi-Engine Consensus Docking Pipeline for RNA Aptamer Screening Against ACC Oxidase (ACO): Statistical Validation, Machine Learning Analysis, and Pilot Cross-Target Evaluation Against ACC Synthase (ACS)"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7764-6309","authenticated-orcid":false,"given":"H\u00e9ctor Ram\u00f3n","family":"Mart\u00ednez-de la Hoya","sequence":"first","affiliation":[{"name":"Division of Research and Postgraduate Studies, Tecnol\u00f3gico Nacional de M\u00e9xico\/I.T. Durango, Blvd. Felipe Pescador 1830, Durango 34080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4676-4762","authenticated-orcid":false,"given":"Cristian Patricia","family":"Cabrales-Arellano","sequence":"additional","affiliation":[{"name":"Department of Biology, Eastern New Mexico University, Portales, NM 88130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5396-2092","authenticated-orcid":false,"given":"Josu\u00e9","family":"Ortiz-Medina","sequence":"additional","affiliation":[{"name":"Division of Research and Postgraduate Studies, Tecnol\u00f3gico Nacional de M\u00e9xico\/I.T. Durango, Blvd. Felipe Pescador 1830, Durango 34080, Mexico"},{"name":"Department of Electrical and Electronics Engineering, Tecnol\u00f3gico Nacional de M\u00e9xico\/I.T. Durango, Blvd. Felipe Pescador 1830, Durango 34080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7359-6309","authenticated-orcid":false,"given":"Efren","family":"Delgado","sequence":"additional","affiliation":[{"name":"Department of Family and Consumer Sciences, New Mexico State University, Las Cruces, NM 88003, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9632-7555","authenticated-orcid":false,"given":"Juan Antonio","family":"Rojas-Contreras","sequence":"additional","affiliation":[{"name":"Division of Research and Postgraduate Studies, Tecnol\u00f3gico Nacional de M\u00e9xico\/I.T. Durango, Blvd. Felipe Pescador 1830, Durango 34080, Mexico"},{"name":"Department of Chemical and Biochemical Engineering, Tecnol\u00f3gico Nacional de M\u00e9xico\/I.T. Durango, Blvd. Felipe Pescador 1830, Durango 34080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2478-5174","authenticated-orcid":false,"given":"Norma A.","family":"Garc\u00eda-Vida\u00f1a","sequence":"additional","affiliation":[{"name":"Division of Research and Postgraduate Studies, Tecnol\u00f3gico Nacional de M\u00e9xico\/I.T. Durango, Blvd. Felipe Pescador 1830, Durango 34080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6033-8965","authenticated-orcid":false,"given":"Dami\u00e1n","family":"Reyes-J\u00e1quez","sequence":"additional","affiliation":[{"name":"Division of Research and Postgraduate Studies, Tecnol\u00f3gico Nacional de M\u00e9xico\/I.T. Durango, Blvd. Felipe Pescador 1830, Durango 34080, Mexico"},{"name":"Department of Chemical and Biochemical Engineering, Tecnol\u00f3gico Nacional de M\u00e9xico\/I.T. Durango, Blvd. Felipe Pescador 1830, Durango 34080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5010-2783","authenticated-orcid":false,"given":"Rub\u00e9n","family":"Guerrero-Rivera","sequence":"additional","affiliation":[{"name":"Division of Research and Postgraduate Studies, Tecnol\u00f3gico Nacional de M\u00e9xico\/I.T. Durango, Blvd. Felipe Pescador 1830, Durango 34080, Mexico"},{"name":"Department of Electrical and Electronics Engineering, Tecnol\u00f3gico Nacional de M\u00e9xico\/I.T. Durango, Blvd. Felipe Pescador 1830, Durango 34080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1146\/annurev.pp.35.060184.001103","article-title":"Ethylene Biosynthesis and Its Regulation in Higher Plants","volume":"35","author":"Yang","year":"1984","journal-title":"Annu. Rev. Plant Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.biotechadv.2006.01.005","article-title":"The Use of 1-Methylcyclopropene (1-MCP) on Fruits and Vegetables","volume":"24","author":"Watkins","year":"2006","journal-title":"Biotechnol. Adv."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1111\/j.1399-3054.1997.tb03063.x","article-title":"Inhibitors of Ethylene Responses in Plants at the Receptor Level: Recent Developments","volume":"100","author":"Sisler","year":"1997","journal-title":"Physiol. Plant."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/346818a0","article-title":"In Vitro Selection of RNA Molecules That Bind Specific Ligands","volume":"346","author":"Ellington","year":"1990","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"113279","DOI":"10.1016\/j.bios.2021.113279","article-title":"Aptamer-Based Lateral Flow Assay On-Site Biosensors","volume":"186","author":"Huang","year":"2021","journal-title":"Biosens. Bioelectron."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"240","DOI":"10.18782\/2582-2845.8214","article-title":"Aptamer Selection: Choosing the Appropriate SELEX","volume":"9","author":"Malhotra","year":"2021","journal-title":"Indian J. Pure Appl. Biosci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Chen, Z., Hu, L., Zhang, B.-T., Lu, A., Wang, Y., Yu, Y., and Zhang, G. (2021). Artificial Intelligence in Aptamer\u2013Target Binding Prediction. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073605"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1126\/science.2200121","article-title":"Systematic Evolution of Ligands by Exponential Enrichment: RNA Ligands to Bacteriophage T4 DNA Polymerase","volume":"249","author":"Tuerk","year":"1990","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.biochi.2020.10.005","article-title":"In Silico Molecular Docking in DNA Aptamer Development","volume":"180","author":"Navien","year":"2021","journal-title":"Biochimie"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lee, S.J., Cho, J., Lee, B.-H., Hwang, D., and Park, J.-W. (2023). Design and Prediction of Aptamers Assisted by In Silico Methods. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020356"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Buglak, A.A., Samokhvalov, A.V., Zherdev, A.V., and Dzantiev, B.B. (2020). Methods and Applications of In Silico Aptamer Design and Modeling. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228420"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Morena, F., Argentati, C., Tortorella, I., Emiliani, C., and Martino, S. (2021). De Novo ssRNA Aptamers against the SARS-CoV-2 Main Protease: In Silico Design and Molecular Dynamics Simulation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136874"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ferreira-Bravo, I.A., and DeStefano, J.J. (2021). Xeno-Nucleic Acid (XNA) 2\u2019-Fluoro-Arabino Nucleic Acid (FANA) Aptamers to the Receptor-Binding Domain of SARS-CoV-2 S Protein Block ACE2 Binding. Viruses, 13.","DOI":"10.1101\/2021.07.13.452259"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8486","DOI":"10.1073\/pnas.1913242117","article-title":"In Silico Design and Validation of High-Affinity RNA Aptamers Targeting Epithelial Cellular Adhesion Molecule Dimers","volume":"117","author":"Bell","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1021\/jacs.3c09733","article-title":"Steric Perturbation of the Grob-like Final Step of Ethylene-Forming Enzyme Enables 3-Hydroxypropionate and Propylene Production","volume":"146","author":"Chatterjee","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1021\/acscatal.0c03349","article-title":"Atomic and Electronic Structure Determinants Distinguish between Ethylene Formation and L-Arginine Hydroxylation Reaction Mechanisms in the Ethylene-Forming Enzyme","volume":"11","author":"Chaturvedi","year":"2021","journal-title":"ACS Catal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3923","DOI":"10.1021\/acscatal.1c04029","article-title":"Cluster Model Study into the Catalytic Mechanism of \u03b1-Ketoglutarate Biodegradation by the Ethylene-Forming Enzyme Reveals Structural Differences with Nonheme Iron Hydroxylases","volume":"12","author":"Yeh","year":"2022","journal-title":"ACS Catal."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Aparicio-Breceda, D.L., Cabrales-Arellano, C.P., Delgado, E., P\u00e1manes-Carrasco, G.A., Gamero-Barraza, J.I., Medrano-Rold\u00e1n, H., and Reyes-J\u00e1quez, D. (2025). Aptamers as Potential Inhibitors of Ethylene Biosynthesis: Identification and In Silico Selection. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26178146"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1006\/jmbi.1999.3255","article-title":"Structure of 1-Aminocyclopropane-1-carboxylate Synthase, a Key Enzyme in the Biosynthesis of the Plant Hormone Ethylene","volume":"294","author":"Capitani","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1016\/j.chembiol.2004.08.012","article-title":"Crystal Structure and Mechanistic Implications of 1-Aminocyclopropane-1-carboxylic Acid Oxidase\u2014The Ethylene-Forming Enzyme","volume":"11","author":"Zhang","year":"2004","journal-title":"Chem. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8835","DOI":"10.1002\/chem.200501459","article-title":"Ethylene Biosynthesis by 1-Aminocyclopropane-1-Carboxylic Acid Oxidase: A DFT Study","volume":"12","author":"Bassan","year":"2006","journal-title":"Chem. Eur. J."},{"key":"ref_22","first-page":"31","article-title":"Characterization of Cu(II)-Reconstituted ACC Oxidase Using Experimental and Theoretical Approaches","volume":"623\u2013624","author":"Tachon","year":"2017","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1007\/s12033-019-00191-5","article-title":"Chemical Modification of 1-Aminocyclopropane Carboxylic Acid (ACC) Oxidase: Cysteine Mutational Analysis, Characterization, and Bioconjugation with a Nitroxide Spin Label","volume":"61","author":"Tachon","year":"2019","journal-title":"Mol. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"15758","DOI":"10.1038\/ncomms15758","article-title":"Pyrazinamide and Derivatives Block Ethylene Biosynthesis by Inhibiting ACC Oxidase","volume":"8","author":"Sun","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"kiag025","DOI":"10.1093\/plphys\/kiag025","article-title":"1-Aminocyclopropane-1-Carboxylic Acid Oxidase Determines the Fate of Ethylene Biosynthesis in a Tissue-Specific Way","volume":"200","author":"Houben","year":"2026","journal-title":"Plant Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e87","DOI":"10.1093\/nar\/gkp408","article-title":"In Silico Selection of RNA Aptamers","volume":"37","author":"Chushak","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1080\/15257770.2021.1951754","article-title":"In Silico Strategies for Modeling RNA Aptamers and Predicting Binding Sites of Their Molecular Targets","volume":"40","year":"2021","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1021\/acs.jcim.9b00756","article-title":"In Silico Design of Novel Mutant Anti-MUC1 Aptamers for Targeted Cancer Therapy","volume":"60","author":"Santini","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100757","DOI":"10.1016\/j.imu.2021.100757","article-title":"In Silico Design of Quadruplex Aptamers against the Spike Protein of SARS-CoV-2","volume":"26","author":"Behbahani","year":"2021","journal-title":"Inform. Med. Unlocked"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.3390\/ijms11083016","article-title":"Advances and Challenges in Protein\u2013Ligand Docking","volume":"11","author":"Huang","year":"2010","journal-title":"Int. J. Mol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Quintela, I.A., Vasse, T., Jian, D., Harrington, C., Sien, W., and Wu, V.C.H. (2025). Elucidating the Molecular Docking and Binding Dynamics of Aptamers with Spike Proteins across SARS-CoV-2 Variants of Concern. Front. Microbiol., 16.","DOI":"10.3389\/fmicb.2025.1503890"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"bbae517","DOI":"10.1093\/bib\/bbae517","article-title":"AptaDiff: De Novo Design and Optimization of Aptamers Based on Diffusion Models","volume":"25","author":"Zhu","year":"2024","journal-title":"Brief. Bioinform."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1073\/pnas.89.6.2195","article-title":"Molecular Surface Recognition: Determination of Geometric Fit between Proteins and Their Ligands by Correlation Techniques","volume":"89","author":"Shariv","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1023\/A:1010933404324","article-title":"Random Forests","volume":"45","author":"Breiman","year":"2001","journal-title":"Mach. Learn."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3973","DOI":"10.1021\/ac900305y","article-title":"Investigations on the Specificity of DNA Aptamers Binding to Ethanolamine","volume":"81","author":"Reinemann","year":"2009","journal-title":"Anal. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1093\/bioinformatics\/btq112","article-title":"A Machine Learning Approach to Predicting Protein\u2013Ligand Binding Affinity with Applications to Molecular Docking","volume":"26","author":"Ballester","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1021\/pr9009854","article-title":"Are Scoring Functions in Protein\u2013Protein Docking Ready to Predict Interactomes? Clues from a Novel Binding Affinity Benchmark","volume":"9","author":"Kastritis","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3104","DOI":"10.1002\/prot.22764","article-title":"Performance of ZDOCK and ZRANK in CAPRI Rounds 13\u201319","volume":"78","author":"Hwang","year":"2010","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated Docking with Selective Receptor Flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1002\/pro.687","article-title":"Integrating Atom-Based and Residue-Based Scoring Functions for Protein\u2013Protein Docking","volume":"20","author":"Vreven","year":"2011","journal-title":"Protein Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"W322","DOI":"10.1093\/nar\/gkz397","article-title":"HawkDock: A Web Server to Predict and Analyze the Protein\u2013Protein Complex Based on Computational Docking and MM\/GBSA","volume":"47","author":"Weng","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1748-7188-6-26","article-title":"ViennaRNA Package 2.0","volume":"6","author":"Lorenz","year":"2011","journal-title":"Algorithms Mol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/BF00818163","article-title":"Fast Folding and Comparison of RNA Secondary Structures","volume":"125","author":"Hofacker","year":"1994","journal-title":"Monatsh. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e112","DOI":"10.1093\/nar\/gks339","article-title":"Automated 3D Structure Composition for Large RNAs","volume":"40","author":"Popenda","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1002\/prot.26578","article-title":"RNA Tertiary Structure Prediction Using RNAComposer in CASP15","volume":"91","author":"Sarzynska","year":"2023","journal-title":"Proteins"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5179","DOI":"10.1021\/ja00124a002","article-title":"A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules","volume":"117","author":"Cornell","year":"1995","journal-title":"J. Am. Chem. Soc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"W365","DOI":"10.1093\/nar\/gkx407","article-title":"HDOCK: A Web Server for Protein\u2013Protein and Protein\u2013DNA\/RNA Docking Based on a Hybrid Strategy","volume":"45","author":"Yan","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e55","DOI":"10.1093\/nar\/gku077","article-title":"A Knowledge-Based Scoring Function for Protein-RNA Interactions Derived from a Statistical Mechanics-Based Iterative Method","volume":"42","author":"Huang","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/prot.21949","article-title":"An Iterative Knowledge-Based Scoring Function for Protein\u2013Protein Recognition","volume":"72","author":"Huang","year":"2008","journal-title":"Proteins"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1038\/s41596-020-0312-x","article-title":"The HDOCK Server for Integrated Protein\u2013Protein Docking","volume":"15","author":"Yan","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/prot.25234","article-title":"Addressing Recent Docking Challenges: A Hybrid Strategy to Integrate Template-Based and Free Protein\u2013Protein Docking","volume":"85","author":"Yan","year":"2017","journal-title":"Proteins"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7315","DOI":"10.1021\/acs.jcim.5c00969","article-title":"HADDOCK3: A Modular and Versatile Platform for Integrative Modeling of Biomolecular Complexes","volume":"65","author":"Giulini","year":"2025","journal-title":"J. Chem. Inf. Model."},{"key":"ref_54","unstructured":"Mart\u00ednez de la Hoya, H.R. (2026). AptaDock: An Integrated Desktop Application for GPU-Accelerated Tripartite RNA Aptamer Docking, Instituto Tecnol\u00f3gico de Durango."},{"key":"ref_55","unstructured":"Laboratorio Nacional de Superc\u00f3mputo del Sureste de M\u00e9xico (LNS-BUAP) Cl\u00faster Huap\u00e1ctic: High-Performance Computing Infrastructure, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla. Available online: https:\/\/lns.buap.mx."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1098\/rspl.1895.0041","article-title":"Note on Regression and Inheritance in the Case of Two Parents","volume":"58","author":"Pearson","year":"1895","journal-title":"Proc. R. Soc. Lond."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"20150202","DOI":"10.1098\/rsta.2015.0202","article-title":"Principal Component Analysis: A Review and Recent Developments","volume":"374","author":"Jolliffe","year":"2016","journal-title":"Philos. Trans. R. Soc. A"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5947\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T14:55:52Z","timestamp":1783004152000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5947"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":57,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27135947"],"URL":"https:\/\/doi.org\/10.3390\/ijms27135947","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,2]]}}}