{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T18:27:27Z","timestamp":1786472847665,"version":"build-2736575974"},"reference-count":82,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007224","name":"Vietnam National Foundation for Science and Technology Development","doi-asserted-by":"crossref","award":["106.02-2023.05"],"award-info":[{"award-number":["106.02-2023.05"]}],"id":[{"id":"10.13039\/100007224","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Breast cancer remains a major cause of morbidity and mortality in women, with around 2.3 million new cases and 670,000 deaths worldwide in 2022. Daidzin, a soy isoflavone glycoside from\n                    <jats:italic>Glycine max<\/jats:italic>\n                    , is a candidate bioactive scaffold, but its breast cancer-relevant mechanisms remain poorly defined. This study used an integrated\n                    <jats:italic>in silico<\/jats:italic>\n                    strategy combining network pharmacology and molecular modeling to prioritize daidzin targets and validate key interactions, with sirtinol as a reference compound. Target prediction identified 101 putative daidzin targets, and intersection with breast cancer-associated genes yielded 97 common targets. Protein-protein interaction analysis highlighted hub genes including ALB, TNF, MMP9, CASP3, SRC, ITGB1, MMP2, ESR1, IL2, and HSP90AA1. Enrichment analyses suggested convergence on extracellular\/vesicle-related functions, metallopeptidase activity, and pathway modules spanning metabolism, inflammation, endocrine signaling, and cancer circuitry. Docking against ten hub proteins produced binding energies from \u22126.00 to \u221211.49 kcal\/mol, with the strongest affinity for MMP9 (6ESM; \u221211.49 kcal\/mol), exceeding B9Z (\u221210.54 kcal\/mol) and sirtinol (\u221210.59 kcal\/mol). Molecular dynamics simulations indicated stable complexes, and Molecular Mechanics Generalized Born Surface Area (MMGBSA) supported stronger binding for daidzin-MMP9 (\u221246.86\u2009\u00b1\u20093.83 kcal\/mol) than sirtinol-MMP9 (\u221214.12\u2009\u00b1\u20098.99 kcal\/mol). Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) prediction indicated favorable safety-related flags for daidzin, although lower predicted intestinal absorption and Caco2 permeability than sirtinol suggest potential exposure-related limitations. Density Functional Theory (DFT) analysis supported comparatively greater electronic stability. Collectively, the results prioritize a daidzin-MMP9 axis for experimental validation.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0355672","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T17:27:20Z","timestamp":1786469240000},"page":"e0355672","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic insights into daidzin from Glycine max against breast cancer via network pharmacology and multi-level molecular modeling"],"prefix":"10.1371","volume":"21","author":[{"given":"Lan Thi","family":"Vu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luong Trong","family":"Vu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lien Thi 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strategies","volume":"99","author":"O Saatci","year":"2021","journal-title":"J Mol Med (Berl)"},{"key":"pone.0355672.ref004","doi-asserted-by":"crossref","first-page":"6331630","DOI":"10.1155\/2021\/6331630","article-title":"Therapeutic Potential of Isoflavones with an Emphasis on Daidzein","volume":"2021","author":"MM Alshehri","year":"2021","journal-title":"Oxid Med Cell Longev"},{"issue":"11","key":"pone.0355672.ref005","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1111\/bph.13622","article-title":"The potential health effects of dietary phytoestrogens","volume":"174","author":"IMCM Rietjens","year":"2017","journal-title":"Br J Pharmacol"},{"issue":"2","key":"pone.0355672.ref006","doi-asserted-by":"crossref","first-page":"556","DOI":"10.21873\/invivo.12737","article-title":"Soy Isoflavones and breast cancer risk: A meta-analysis","volume":"36","author":"I Boutas","year":"2022","journal-title":"In Vivo"},{"issue":"2","key":"pone.0355672.ref007","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1002\/ptr.8417","article-title":"Exploring the complex mechanisms of isoflavones: from cell bioavailability, to cell dynamics and breast cancer","volume":"39","author":"F Ferriere","year":"2025","journal-title":"Phytother Res"},{"issue":"14","key":"pone.0355672.ref008","doi-asserted-by":"crossref","first-page":"6973","DOI":"10.3390\/ijms26146973","article-title":"Daidzein and genistein: Natural phytoestrogens with potential applications in hormone replacement therapy","volume":"26","author":"A Intharuksa","year":"2025","journal-title":"Int J Mol Sci"},{"issue":"5","key":"pone.0355672.ref009","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1073\/pnas.94.5.1675","article-title":"Daidzin inhibits mitochondrial aldehyde dehydrogenase and suppresses ethanol intake of Syrian golden hamsters","volume":"94","author":"WM Keung","year":"1997","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"pone.0355672.ref010","doi-asserted-by":"crossref","DOI":"10.1002\/mgg3.707","article-title":"The functional ALDH2 polymorphism is associated with breast cancer risk: A pooled analysis from the Breast Cancer Association Consortium","volume":"7","author":"T Ugai","year":"2019","journal-title":"Mol Genet Genomic Med"},{"issue":"1","key":"pone.0355672.ref011","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/s12885-021-07860-2","article-title":"Prognostic values of tumoral MMP2 and MMP9 overexpression in breast cancer: A systematic review and meta-analysis","volume":"21","author":"H Jiang","year":"2021","journal-title":"BMC Cancer"},{"issue":"1","key":"pone.0355672.ref012","doi-asserted-by":"crossref","first-page":"14","DOI":"10.4161\/cbt.13.1.18869","article-title":"Tumor microenvironment and breast cancer progression","volume":"13","author":"A Artacho-Cord\u00f3n","year":"2012","journal-title":"Cancer Biology & Therapy"},{"issue":"1","key":"pone.0355672.ref013","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12943-023-01744-8","article-title":"Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments","volume":"22","author":"Z Yuan","year":"2023","journal-title":"Mol Cancer"},{"issue":"1","key":"pone.0355672.ref014","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1186\/s13046-024-03218-1","article-title":"Understanding the role of TNFR2 signaling in the tumor microenvironment of breast cancer","volume":"43","author":"A Mussa","year":"2024","journal-title":"J Exp Clin Cancer Res"},{"issue":"16","key":"pone.0355672.ref015","doi-asserted-by":"crossref","first-page":"4790","DOI":"10.1158\/1078-0432.CCR-06-1535","article-title":"Estrogen receptor pathway: Resistance to endocrine therapy and new therapeutic approaches","volume":"12","author":"B Moy","year":"2006","journal-title":"Clin Cancer Res"},{"issue":"8","key":"pone.0355672.ref016","doi-asserted-by":"crossref","first-page":"939","DOI":"10.4155\/fmc.12.44","article-title":"Network pharmacology for cancer drug discovery: Are we there yet?","volume":"4","author":"AS Azmi","year":"2012","journal-title":"Future Med Chem"},{"key":"pone.0355672.ref017","first-page":"1","article-title":"Bioisosteric coumarin\u2013pyrimidine hybrids for multi-target breast-cancer inhibition: An integrated in silico study","author":"VB Hacholli","year":"2026","journal-title":"Chem Pap"},{"issue":"1","key":"pone.0355672.ref018","doi-asserted-by":"crossref","first-page":"81","DOI":"10.15625\/vjbt-23376","article-title":"Investigation of soyasapogenols from soybean seed germs as Anti-apoptotic agents in colon cancer using an In silico approach","volume":"24","author":"TL Vu","year":"2026","journal-title":"Vietnam J Biotechnol"},{"issue":"12","key":"pone.0355672.ref019","article-title":"Combining machine learning systems and multiple docking simulation packages to improve docking prediction reliability for network pharmacology","volume":"8","author":"K-Y Hsin","year":"2013","journal-title":"PLoS One"},{"issue":"2","key":"pone.0355672.ref020","doi-asserted-by":"crossref","first-page":"298","DOI":"10.3390\/pr10020298","article-title":"Implementation of system pharmacology and molecular docking approaches to explore active compounds and mechanism of Ocimum Sanctum against tuberculosis","volume":"10","author":"S Tabassum","year":"2022","journal-title":"Processes"},{"issue":"11","key":"pone.0355672.ref021","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"P Shannon","year":"2003","journal-title":"Genome Res"},{"key":"pone.0355672.ref022","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkab835","article-title":"The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"D Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pone.0355672.ref023","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s11693-013-9123-5","article-title":"The organisational structure of protein networks: Revisiting the centrality-lethality hypothesis","volume":"8","author":"K Raman","year":"2014","journal-title":"Syst Synth Biol"},{"issue":"4","key":"pone.0355672.ref024","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1000350","article-title":"Information flow analysis of interactome networks","volume":"5","author":"PV Missiuro","year":"2009","journal-title":"PLoS Comput Biol"},{"key":"pone.0355672.ref025","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.biosystems.2014.11.005","article-title":"CytoNCA: A cytoscape plugin for centrality analysis and evaluation of protein interaction networks","volume":"127","author":"Y Tang","year":"2015","journal-title":"Biosystems"},{"issue":"1","key":"pone.0355672.ref026","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1186\/s12885-021-08412-4","article-title":"Bioinformatics analysis of differentially expressed genes and pathways in the development of cervical cancer","volume":"21","author":"B Wu","year":"2021","journal-title":"BMC Cancer"},{"issue":"16","key":"pone.0355672.ref027","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1002\/jcc.20291","article-title":"GROMACS: Fast, flexible, and free","volume":"26","author":"D Van Der Spoel","year":"2005","journal-title":"J Comput Chem"},{"issue":"15","key":"pone.0355672.ref028","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1002\/elps.1150181505","article-title":"SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modeling","volume":"18","author":"N Guex","year":"1997","journal-title":"Electrophoresis"},{"issue":"11","key":"pone.0355672.ref029","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1002\/jcc.21816","article-title":"SwissParam: A fast force field generation tool for small organic molecules","volume":"32","author":"V Zoete","year":"2011","journal-title":"J Comput Chem"},{"issue":"20","key":"pone.0355672.ref030","doi-asserted-by":"crossref","first-page":"10096","DOI":"10.1063\/1.1808117","article-title":"A modified TIP3P water potential for simulation with Ewald summation","volume":"121","author":"DJ Price","year":"2004","journal-title":"J Chem Phys"},{"key":"pone.0355672.ref031","doi-asserted-by":"crossref","first-page":"104692","DOI":"10.1016\/j.compbiomed.2021.104692","article-title":"Tracking the interaction between single-wall carbon nanotube and SARS-Cov-2 spike glycoprotein: A molecular dynamics simulations study","volume":"136","author":"M Jomhori","year":"2021","journal-title":"Comput Biol Med"},{"issue":"5","key":"pone.0355672.ref032","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1021\/acschemneuro.7b00490","article-title":"What Contributes to Serotonin-Norepinephrine Reuptake Inhibitors\u2019 Dual-Targeting Mechanism? The Key Role of Transmembrane Domain 6 in Human Serotonin and Norepinephrine Transporters Revealed by Molecular Dynamics Simulation","volume":"9","author":"W Xue","year":"2018","journal-title":"ACS Chem Neurosci"},{"issue":"9","key":"pone.0355672.ref033","doi-asserted-by":"crossref","first-page":"6606","DOI":"10.1039\/C7CP07869B","article-title":"Computational identification of the binding mechanism of a triple reuptake inhibitor amitifadine for the treatment of major depressive disorder","volume":"20","author":"W Xue","year":"2018","journal-title":"Phys Chem Chem Phys"},{"issue":"9","key":"pone.0355672.ref034","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures","volume":"58","author":"DEV Pires","year":"2015","journal-title":"J Med Chem"},{"issue":"5","key":"pone.0355672.ref035","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","article-title":"The MM\/PBSA and MM\/GBSA methods to estimate ligand-binding affinities","volume":"10","author":"S Genheden","year":"2015","journal-title":"Expert Opin Drug Discov"},{"issue":"11","key":"pone.0355672.ref036","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s00894-025-06487-5","article-title":"Conceptual density functional theory in drug discovery: An overview","volume":"31","author":"H Rohit","year":"2025","journal-title":"J Mol Model"},{"key":"pone.0355672.ref037","doi-asserted-by":"crossref","DOI":"10.1002\/wcms.70019","article-title":"Software update: The ORCA program system-version 6.0","volume":"15","author":"F Neese","year":"2025","journal-title":"WIREs Comput Mol Sci"},{"issue":"18","key":"pone.0355672.ref038","doi-asserted-by":"crossref","first-page":"5518","DOI":"10.1002\/anie.201410637","article-title":"Electron flow in reaction mechanisms--revealed from first principles","volume":"54","author":"G Knizia","year":"2015","journal-title":"Angew Chem Int Ed Engl"},{"issue":"11","key":"pone.0355672.ref039","doi-asserted-by":"crossref","first-page":"4834","DOI":"10.1021\/ct400687b","article-title":"Intrinsic atomic orbitals: An unbiased bridge between quantum theory and chemical concepts","volume":"9","author":"G Knizia","year":"2013","journal-title":"J Chem Theory Comput"},{"issue":"1","key":"pone.0355672.ref040","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1758-2946-4-17","article-title":"Avogadro: An advanced semantic chemical editor, visualization, and analysis platform","volume":"4","author":"MD Hanwell","year":"2012","journal-title":"J Cheminform"},{"issue":"43","key":"pone.0355672.ref041","doi-asserted-by":"crossref","first-page":"12005","DOI":"10.1021\/jp063669m","article-title":"Koopmans\u2019 theorem for large molecular systems within density functional theory","volume":"110","author":"J Luo","year":"2006","journal-title":"J Phys Chem A"},{"issue":"21","key":"pone.0355672.ref042","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1002\/qua.24706","article-title":"Chemical reactivity through structure-stability landscape","volume":"114","author":"R Das","year":"2014","journal-title":"Int J Quantum Chem"},{"issue":"4","key":"pone.0355672.ref043","first-page":"558","article-title":"Network pharmacology for traditional Chinese medicine in era of artificial intelligence","volume":"16","author":"W Zhao","year":"2024","journal-title":"Chin Herb Med"},{"key":"pone.0355672.ref044","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jare.2024.12.004","article-title":"Unlocking biological insights from differentially expressed genes: Concepts, methods, and future perspectives","volume":"76","author":"H Yin","year":"2025","journal-title":"J Adv Res"},{"key":"pone.0355672.ref045","doi-asserted-by":"crossref","first-page":"838133","DOI":"10.3389\/fphar.2022.838133","article-title":"Targeting angiogenesis in breast cancer: Current evidence and future perspectives of novel anti-angiogenic approaches","volume":"13","author":"NM Ayoub","year":"2022","journal-title":"Front Pharmacol"},{"issue":"2","key":"pone.0355672.ref046","doi-asserted-by":"crossref","DOI":"10.1002\/ctm2.308","article-title":"Understanding cell-cell communication and signaling in the colorectal cancer microenvironment","volume":"11","author":"S AlMusawi","year":"2021","journal-title":"Clin Transl Med"},{"key":"pone.0355672.ref047","doi-asserted-by":"crossref","first-page":"650453","DOI":"10.3389\/fonc.2021.650453","article-title":"Extracellular matrix: Emerging roles and potential therapeutic targets for breast cancer","volume":"11","author":"Y Zhao","year":"2021","journal-title":"Front Oncol"},{"issue":"5","key":"pone.0355672.ref048","doi-asserted-by":"crossref","first-page":"654","DOI":"10.3390\/pharmaceutics16050654","article-title":"Extracellular vesicles in breast cancer: from intercellular communication to therapeutic opportunities","volume":"16","author":"B Muttiah","year":"2024","journal-title":"Pharmaceutics"},{"issue":"5","key":"pone.0355672.ref049","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1194\/jlr.TR119000439","article-title":"Lipid rafts as signaling hubs in cancer cell survival\/death and invasion: implications in tumor progression and therapy: Thematic Review Series: Biology of Lipid Rafts","volume":"61","author":"F Mollinedo","year":"2020","journal-title":"J Lipid Res"},{"issue":"2","key":"pone.0355672.ref050","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41416-019-0642-z","article-title":"Carbonic anhydrase IX and acid transport in cancer","volume":"122","author":"HM Becker","year":"2020","journal-title":"Br J Cancer"},{"key":"pone.0355672.ref051","doi-asserted-by":"crossref","first-page":"1201632","DOI":"10.3389\/fimmu.2023.1201632","article-title":"The immune checkpoint adenosine 2A receptor is associated with aggressive clinical outcomes and reflects an immunosuppressive tumor microenvironment in human breast cancer","volume":"14","author":"B Zohair","year":"2023","journal-title":"Front Immunol"},{"key":"pone.0355672.ref052","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkw1092","article-title":"KEGG: New perspectives on genomes, pathways, diseases and drugs","volume":"45","author":"M Kanehisa","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"pone.0355672.ref053","doi-asserted-by":"crossref","first-page":"749","DOI":"10.3389\/fcell.2020.00749","article-title":"The role of proteoglycans in cancer metastasis and circulating tumor cell analysis","volume":"8","author":"TD Ahrens","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"pone.0355672.ref054","doi-asserted-by":"crossref","first-page":"699478","DOI":"10.3389\/fimmu.2021.699478","article-title":"\u201c\u03b3\u03b4T Cell-IL17A-Neutrophil\u201d Axis drives immunosuppression and confers breast cancer resistance to high-dose Anti-VEGFR2 therapy","volume":"12","author":"Z Zhang","year":"2021","journal-title":"Front Immunol"},{"key":"pone.0355672.ref055","doi-asserted-by":"crossref","first-page":"114822","DOI":"10.1016\/j.biopha.2023.114822","article-title":"The role of NF-\u03baB in breast cancer initiation, growth, metastasis, and resistance to chemotherapy","volume":"163","author":"E Pavitra","year":"2023","journal-title":"Biomed Pharmacother"},{"key":"pone.0355672.ref056","doi-asserted-by":"crossref","first-page":"599586","DOI":"10.3389\/fendo.2021.599586","article-title":"Molecular mechanisms of endocrine resistance in estrogen-positive breast cancer","volume":"12","author":"EB Belachew","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"pone.0355672.ref057","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/s42003-021-02648-3","article-title":"Hypoxia inducible factor signaling in breast tumors controls spontaneous tumor dissemination in a site-specific manner","volume":"4","author":"VM Todd","year":"2021","journal-title":"Commun Biol"},{"issue":"11","key":"pone.0355672.ref058","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.3390\/molecules26113171","article-title":"The role of serotonin in breast cancer stem cells","volume":"26","author":"WD Gwynne","year":"2021","journal-title":"Molecules"},{"issue":"3","key":"pone.0355672.ref059","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.3390\/ijms24032107","article-title":"The critical impact of sphingolipid metabolism in breast cancer progression and drug response","volume":"24","author":"PA Corsetto","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"2","key":"pone.0355672.ref060","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1055\/s-0043-1768166","article-title":"The role of the matrix metalloproteinase-9 gene in tumor development and metastasis: A narrative review","volume":"10","author":"D Kalali","year":"2023","journal-title":"Glob Med Genet"},{"issue":"1","key":"pone.0355672.ref061","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1186\/s12967-023-04696-1","article-title":"The characteristics and the multiple functions of integrin \u03b21 in human cancers","volume":"21","author":"L Sun","year":"2023","journal-title":"J Transl Med"},{"issue":"10","key":"pone.0355672.ref062","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1038\/s41416-024-02875-5","article-title":"The SRC-family serves as a therapeutic target in triple negative breast cancer with acquired resistance to chemotherapy","volume":"131","author":"EV Egeland","year":"2024","journal-title":"Br J Cancer"},{"issue":"5","key":"pone.0355672.ref063","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1080\/1120009X.2023.2278014","article-title":"Recent advances in caspase-3, breast cancer, and traditional Chinese medicine: A review","volume":"36","author":"H Dou","year":"2024","journal-title":"J Chemother"},{"key":"pone.0355672.ref064","doi-asserted-by":"crossref","first-page":"104539","DOI":"10.1016\/j.ebiom.2023.104539","article-title":"A systematic review of interleukin-2-based immunotherapies in clinical trials for cancer and autoimmune diseases","volume":"90","author":"ME Raeber","year":"2023","journal-title":"EBioMedicine"},{"issue":"1","key":"pone.0355672.ref065","first-page":"6","article-title":"HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review)","volume":"49","author":"Z-N Li","year":"2023","journal-title":"Oncol Rep"},{"key":"pone.0355672.ref066","first-page":"2877","article-title":"Unveiling the mechanism of genistin from Glycine max against breast cancer using computational approaches","volume":"80","author":"LT Vu","year":"2025","journal-title":"Chem Pap"},{"issue":"18","key":"pone.0355672.ref067","doi-asserted-by":"crossref","first-page":"3949","DOI":"10.3390\/nu15183949","article-title":"Integrated Network Pharmacology, Molecular Docking, Molecular Simulation, and In Vitro Validation Revealed the Bioactive Components in Soy-Fermented Food Products and the Underlying Mechanistic Pathways in Lung Cancer","volume":"15","author":"AEO Elkhalifa","year":"2023","journal-title":"Nutrients"},{"key":"pone.0355672.ref068","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/B978-0-12-821978-2.00115-X","article-title":"Interactive molecular dynamics.","volume-title":"Comprehensive computational chemistry","author":"A Lanrezac","year":"2024"},{"issue":"1","key":"pone.0355672.ref069","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3390\/pr9010071","article-title":"Molecular dynamics simulations in drug discovery and pharmaceutical development","volume":"9","author":"OMH Salo-Ahen","year":"2020","journal-title":"Processes"},{"issue":"3","key":"pone.0355672.ref070","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.1501240","article-title":"Regulation of protein-ligand binding affinity by hydrogen bond pairing","volume":"2","author":"D Chen","year":"2016","journal-title":"Sci Adv"},{"key":"pone.0355672.ref071","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1039\/D1ME00053E","article-title":"On the estimation of the molecular inaccessible volume and the molecular accessible surface of a ligand in protein-ligand systems","volume":"6","author":"K Konstantinidis","year":"2021","journal-title":"Molecular Systems Design & Engineering"},{"issue":"21","key":"pone.0355672.ref072","doi-asserted-by":"crossref","first-page":"14450","DOI":"10.1039\/C7CP07623A","article-title":"Assessing the performance of MM\/PBSA and MM\/GBSA methods. 7. Entropy effects on the performance of end-point binding free energy calculation approaches","volume":"20","author":"H Sun","year":"2018","journal-title":"Phys Chem Chem Phys"},{"issue":"7","key":"pone.0355672.ref073","doi-asserted-by":"crossref","first-page":"4240","DOI":"10.1039\/C9CP06459A","article-title":"Improving the performance of the MM\/PBSA and MM\/GBSA methods in recognizing the native structure of the Bcl-2 family using the interaction entropy method","volume":"22","author":"S Zhong","year":"2020","journal-title":"Phys Chem Chem Phys"},{"issue":"4","key":"pone.0355672.ref074","doi-asserted-by":"crossref","DOI":"10.1002\/wcms.1455","article-title":"Ligand binding free energy and kinetics calculation in 2020","volume":"10","author":"V Limongelli","year":"2020","journal-title":"WIREs Comput Mol Sci"},{"issue":"1","key":"pone.0355672.ref075","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13321-022-00639-y","article-title":"Predicting the mutation effects of protein-ligand interactions via end-point binding free energy calculations: Strategies and analyses","volume":"14","author":"Y Yu","year":"2022","journal-title":"J Cheminform"},{"issue":"7","key":"pone.0355672.ref076","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.3390\/pharmaceutics13071103","article-title":"Pharmaceutical formulations with P-glycoprotein inhibitory effect as promising approaches for enhancing oral drug absorption and bioavailability","volume":"13","author":"T-T-L Nguyen","year":"2021","journal-title":"Pharmaceutics"},{"issue":"9","key":"pone.0355672.ref077","doi-asserted-by":"crossref","first-page":"10429","DOI":"10.3390\/molecules170910429","article-title":"Computational prediction of blood-brain barrier permeability using decision tree induction","volume":"17","author":"C Suenderhauf","year":"2012","journal-title":"Molecules"},{"issue":"1","key":"pone.0355672.ref078","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4062\/biomolther.2021.102","article-title":"Inhibition of cytochrome P450 enzymes by drugs-molecular basis and practical applications","volume":"30","author":"FP Guengerich","year":"2022","journal-title":"Biomol Ther (Seoul)"},{"key":"pone.0355672.ref079","doi-asserted-by":"crossref","first-page":"951083","DOI":"10.3389\/fphar.2022.951083","article-title":"Ligand-based prediction of hERG-mediated cardiotoxicity based on the integration of different machine learning techniques","volume":"13","author":"P Delre","year":"2022","journal-title":"Front Pharmacol"},{"issue":"12","key":"pone.0355672.ref080","doi-asserted-by":"crossref","first-page":"3678","DOI":"10.3390\/molecules27123678","article-title":"Application of pharmacokinetic prediction platforms in the design of optimized anti-cancer drugs","volume":"27","author":"TC Beck","year":"2022","journal-title":"Molecules"},{"key":"pone.0355672.ref081","doi-asserted-by":"crossref","first-page":"929464","DOI":"10.3389\/fchem.2022.929464","article-title":"Molecular interactions from the density functional theory for chemical reactivity: Interaction chemical potential, hardness, and reactivity principles","volume":"10","author":"RA Miranda-Quintana","year":"2022","journal-title":"Front Chem"},{"key":"pone.0355672.ref082","doi-asserted-by":"crossref","first-page":"102870","DOI":"10.1016\/j.sbi.2024.102870","article-title":"Quantum mechanical-based strategies in drug discovery: Finding the pace to new challenges in drug design","volume":"87","author":"T Ginex","year":"2024","journal-title":"Curr Opin Struct Biol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0355672","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T17:27:35Z","timestamp":1786469255000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0355672"}},"subtitle":[],"editor":[{"given":"Gayathiri","family":"Ekambaram","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":82,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0355672","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]}}}