{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T07:09:35Z","timestamp":1778310575504,"version":"3.51.4"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Secretariat of Science, Humanities, Technology, and Innovation","award":["637276"],"award-info":[{"award-number":["637276"]}]},{"name":"Secretariat of Science, Humanities, Technology, and Innovation","award":["712505"],"award-info":[{"award-number":["712505"]}]},{"name":"Secretariat of Science, Humanities, Technology, and Innovation","award":["A1-S-17090 (SEP-CONACYT-CB2017-2018)"],"award-info":[{"award-number":["A1-S-17090 (SEP-CONACYT-CB2017-2018)"]}]},{"DOI":"10.13039\/100008989","name":"Autonomous University of Queretaro","doi-asserted-by":"crossref","award":["FONFIVE-UAQ 2025 FQU202561"],"award-info":[{"award-number":["FONFIVE-UAQ 2025 FQU202561"]}],"id":[{"id":"10.13039\/100008989","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Model"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1007\/s00894-026-06729-0","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T08:20:41Z","timestamp":1777278041000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In silico evaluation of selected triterpenes as potential inhibitors of BRAF and BRAFV600E kinases for cancer treatment"],"prefix":"10.1007","volume":"32","author":[{"given":"Giovanny","family":"Aguilera-Dur\u00e1n","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Rivera-Vargas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Hern\u00e1ndez-Estrada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. M.","family":"Alvarez-Baltazar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenda V.","family":"Loera-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma Del Refugio","family":"Cuevas-Flores","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Romo-Mancillas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"6729_CR1","doi-asserted-by":"publisher","first-page":"3183","DOI":"10.1038\/s41388-018-0171-x","volume":"37","author":"M Dankner","year":"2018","unstructured":"Dankner M, Rose AAN, Rajkumar S, Siegel PM, Watson IR (2018) Classifying BRAF alterations in cancer: new rational therapeutic strategies for actionable mutations. Oncogene 37:3183\u20133199. https:\/\/doi.org\/10.1038\/s41388-018-0171-x","journal-title":"Oncogene"},{"key":"6729_CR2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26083757","volume":"26","author":"H Mechahougui","year":"2025","unstructured":"Mechahougui H, Gutmans J, Gouasmi R, Smekens L, Friedlaender A (2025) BRAF targeting across solid tumors: molecular aspects and clinical applications. Int J Mol Sci 26:3757. https:\/\/doi.org\/10.3390\/ijms26083757","journal-title":"Int J Mol Sci"},{"key":"6729_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2022.102205","volume":"71","author":"A Gunderwala","year":"2022","unstructured":"Gunderwala A, Cope N, Wang Z (2022) Mechanism and inhibition of BRAF kinase. Curr Opin Chem Biol 71:102205. https:\/\/doi.org\/10.1016\/j.cbpa.2022.102205","journal-title":"Curr Opin Chem Biol"},{"key":"6729_CR4","doi-asserted-by":"publisher","first-page":"4599","DOI":"10.1158\/1078-0432.CCR-20-1024","volume":"26","author":"JE Chu","year":"2020","unstructured":"Chu JE, Johnson B, Kugathasan L, Morris VK, Raghav K, Swanson L, Lim HJ, Renouf DJ, Gill S, Wolber R, Karsan A, Kopetz S, Schaeffer DF, Loree JM (2020) Population-based screening for BRAF V600E in metastatic colorectal cancer reveals increased prevalence and poor prognosis. Clin Cancer Res 26:4599\u20134605. https:\/\/doi.org\/10.1158\/1078-0432.CCR-20-1024","journal-title":"Clin Cancer Res"},{"key":"6729_CR5","doi-asserted-by":"publisher","first-page":"3574","DOI":"10.1200\/JCO.2011.35.9638","volume":"29","author":"A Marchetti","year":"2011","unstructured":"Marchetti A, Felicioni L, Malatesta S, Grazia Sciarrotta M, Guetti L, Chella A, Viola P, Pullara C, Mucilli F, Buttitta F (2011) Clinical features and outcome of patients with non\u2013small-cell lung cancer harboring BRAF mutations. J Clin Oncol 29:3574\u20133579. https:\/\/doi.org\/10.1200\/JCO.2011.35.9638","journal-title":"J Clin Oncol"},{"key":"6729_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cancers15092607","volume":"15","author":"L Florent","year":"2023","unstructured":"Florent L, Saby C, Slimano F, Morjani H (2023) BRAF V600-mutated metastatic melanoma and targeted therapy resistance: an update of the current knowledge. Cancers (Basel) 15:1\u201313. https:\/\/doi.org\/10.3390\/cancers15092607","journal-title":"Cancers (Basel)"},{"key":"6729_CR7","doi-asserted-by":"publisher","DOI":"10.1007\/s00894-024-06165-y","volume":"30","author":"G Aguilera-Dur\u00e1n","year":"2024","unstructured":"Aguilera-Dur\u00e1n G, Hern\u00e1ndez-Castro S, Loera-Garc\u00eda BV, Rivera-Vargas A, Alvarez-Baltazar JM, Cuevas-Flores MDR, Romo-Mancillas A (2024) Ursolic acid interaction with transcription factors BRAF, V600E, and V600K: a computational approach towards new potential melanoma treatments. J Mol Model 30:373. https:\/\/doi.org\/10.1007\/s00894-024-06165-y","journal-title":"J Mol Model"},{"key":"6729_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2024.104276","volume":"196","author":"A Boutros","year":"2024","unstructured":"Boutros A, Croce E, Ferrari M, Gili R, Massaro G, Marconcini R, Arecco L, Tanda ET, Spagnolo F (2024) The treatment of advanced melanoma: current approaches and new challenges. Crit Rev Oncol Hematol 196:104276. https:\/\/doi.org\/10.1016\/j.critrevonc.2024.104276","journal-title":"Crit Rev Oncol Hematol"},{"key":"6729_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cancers14194863","volume":"14","author":"V Sforza","year":"2022","unstructured":"Sforza V, Palumbo G, Cascetta P, Carillio G, Manzo A, Montanino A, Sandomenico C, Costanzo R, Esposito G, Laudato F, Damiano S, Forte CA, Frosini G, Farese S, Piccirillo MC, Pascarella G, Normanno N, Morabito A (2022) BRAF inhibitors in non-small cell lung cancer. Cancers (Basel) 14:1\u201312. https:\/\/doi.org\/10.3390\/cancers14194863","journal-title":"Cancers (Basel)"},{"key":"6729_CR10","doi-asserted-by":"publisher","first-page":"2876","DOI":"10.1021\/acschembio.6b00529","volume":"11","author":"M Grasso","year":"2016","unstructured":"Grasso M, Estrada MA, Ventocilla C, Samanta M, Maksimoska J, Villanueva J, Winkler JD, Marmorstein R (2016) Chemically linked vemurafenib inhibitors promote an inactive BRAFV600E conformation. ACS Chem Biol 11:2876\u20132888. https:\/\/doi.org\/10.1021\/acschembio.6b00529","journal-title":"ACS Chem Biol"},{"key":"6729_CR11","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1158\/1535-7163.MCT-15-0617","volume":"15","author":"IC Waizenegger","year":"2016","unstructured":"Waizenegger IC, Baum A, Steurer S, Stadtm\u00fcller H, Bader G, Schaaf O, Garin-Chesa P, Schlattl A, Schweifer N, Haslinger C, Colbatzky F, Mousa S, Kalkuhl A, Kraut N, Adolf GR (2016) A novel RAF kinase inhibitor with DFG-out-binding mode: high efficacy in BRAF-mutant tumor xenograft models in the absence of normal tissue hyperproliferation. Mol Cancer Ther 15:354\u2013365. https:\/\/doi.org\/10.1158\/1535-7163.MCT-15-0617","journal-title":"Mol Cancer Ther"},{"key":"6729_CR12","doi-asserted-by":"publisher","first-page":"2249","DOI":"10.1158\/1078-0432.CCR-13-1610","volume":"20","author":"CM Lovly","year":"2014","unstructured":"Lovly CM, Shaw AT (2014) Molecular pathways: resistance to kinase inhibitors and implications for therapeutic strategies. Clin Cancer Res 20:2249\u20132256. https:\/\/doi.org\/10.1158\/1078-0432.CCR-13-1610","journal-title":"Clin Cancer Res"},{"key":"6729_CR13","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1055\/s-0029-1186102","volume":"75","author":"MN Laszczyk","year":"2009","unstructured":"Laszczyk MN (2009) Pentacyclic triterpenes of the lupane, oleanane and ursane group as tools in cancer therapy. Planta Med 75:1549\u20131560. https:\/\/doi.org\/10.1055\/s-0029-1186102","journal-title":"Planta Med"},{"key":"6729_CR14","doi-asserted-by":"publisher","first-page":"39436","DOI":"10.1039\/d4ra07602h","volume":"14","author":"LR Zeng","year":"2024","unstructured":"Zeng LR, Pan BW, Cai J, Liu LJ, Dong ZC, Zhou Y, Feng TT, Shi Y (2024) Construction, structural modification, and bioactivity evaluation of pentacyclic triterpenoid privileged scaffolds in active natural products. RSC Adv 14:39436\u201339461. https:\/\/doi.org\/10.1039\/d4ra07602h","journal-title":"RSC Adv"},{"key":"6729_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.111653","volume":"182","author":"J Hodon","year":"2019","unstructured":"Hodon J, Borkova L, Pokorny J, Kazakova A, Urban M (2019) Design and synthesis of pentacyclic triterpene conjugates and their use in medicinal research. Eur J Med Chem 182:111653. https:\/\/doi.org\/10.1016\/j.ejmech.2019.111653","journal-title":"Eur J Med Chem"},{"key":"6729_CR16","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22030400","author":"NAJC Furtado","year":"2017","unstructured":"Furtado NAJC, Pirson L, Miranda LM, Loira-pastoriza C, Preat V, Larondelle Y, Andr CM (2017) Pentacyclic triterpene bioavailability\u202f: an overview of in vitro and in vivo studies. Molecules. https:\/\/doi.org\/10.3390\/molecules22030400","journal-title":"Molecules"},{"key":"6729_CR17","doi-asserted-by":"publisher","first-page":"2990","DOI":"10.1021\/acs.jctc.6b00201","volume":"12","author":"AJ Clark","year":"2016","unstructured":"Clark AJ, Tiwary P, Borrelli K, Feng S, Miller EB, Abel R, Friesner RA, Berne BJ (2016) Prediction of protein-ligand binding poses via a combination of induced fit docking and metadynamics simulations. J Chem Theory Comput 12:2990\u20132998","journal-title":"J Chem Theory Comput"},{"key":"6729_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-022-05875-8","volume":"12","author":"J Wang","year":"2022","unstructured":"Wang J, Ishchenko A, Zhang W, Razavi A, Langley D (2022) A highly accurate metadynamics-based dissociation free energy method to calculate protein\u2013protein and protein\u2013ligand binding potencies. Sci Rep 12:1\u201311. https:\/\/doi.org\/10.1038\/s41598-022-05875-8","journal-title":"Sci Rep"},{"key":"6729_CR19","doi-asserted-by":"publisher","first-page":"D1373","DOI":"10.1093\/nar\/gkac956","volume":"51","author":"S Kim","year":"2023","unstructured":"Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, Li Q, Shoemaker BA, Thiessen PA, Yu B, Zaslavsky L, Zhang J, Bolton EE (2023) PubChem 2023 update. Nucleic Acids Res 51:D1373\u2013D1380. https:\/\/doi.org\/10.1093\/nar\/gkac956","journal-title":"Nucleic Acids Res"},{"key":"6729_CR20","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","volume":"30","author":"GM Morris","year":"2009","unstructured":"Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30:2785\u20132791. https:\/\/doi.org\/10.1002\/jcc.21256","journal-title":"J Comput Chem"},{"key":"6729_CR21","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1021\/acs.jctc.0c01006","volume":"17","author":"D Santos-Martins","year":"2021","unstructured":"Santos-Martins D, Solis-Vasquez L, Tillack AF, Sanner MF, Koch A, Forli S (2021) Accelerating AutoDock4 with GPUs and gradient-based local search. J Chem Theory Comput 17:1060\u20131073. https:\/\/doi.org\/10.1021\/acs.jctc.0c01006","journal-title":"J Chem Theory Comput"},{"key":"6729_CR22","unstructured":"Schr\u00f6dinger Release 2020\u20131: Desmond molecular dynamics system, D. E. Shaw Research, New York, NY, 2020. Maestro-Desmond interoperability tools, Schr\u00f6dinger, New York, NY 2020. Maestro 2020"},{"key":"6729_CR23","doi-asserted-by":"publisher","first-page":"3684","DOI":"10.1063\/1.448118","volume":"81","author":"HJC Berendsen","year":"1984","unstructured":"Berendsen HJC, Postma JPM, Van Gunsteren WF, Dinola A, Haak JR (1984) Molecular dynamics with coupling to an external bath. J Chem Phys 81:3684\u20133690. https:\/\/doi.org\/10.1063\/1.448118","journal-title":"J Chem Phys"},{"key":"6729_CR24","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/0009-2614(84)80098-6","volume":"105","author":"A Br\u00fcnger","year":"1984","unstructured":"Br\u00fcnger A, Brooks CL, Karplus M (1984) Stochastic boundary conditions for molecular dynamics simulations of ST2 water. Chem Phys Lett 105:495\u2013500. https:\/\/doi.org\/10.1016\/0009-2614(84)80098-6","journal-title":"Chem Phys Lett"},{"key":"6729_CR25","doi-asserted-by":"publisher","DOI":"10.1063\/1.4901303","author":"N Gr\u00f8nbech-Jensen","year":"2014","unstructured":"Gr\u00f8nbech-Jensen N, Farago O (2014) Constant pressure and temperature discrete-time Langevin molecular dynamics. J Chem Phys. https:\/\/doi.org\/10.1063\/1.4901303","journal-title":"J Chem Phys"},{"key":"6729_CR26","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1063\/1.447334","volume":"81","author":"S Nos\u00e9","year":"1984","unstructured":"Nos\u00e9 S (1984) A unified formulation of the constant temperature molecular dynamics methods. J Chem Phys 81:511\u2013519. https:\/\/doi.org\/10.1063\/1.447334","journal-title":"J Chem Phys"},{"key":"6729_CR27","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1103\/PhysRevA.31.1695","volume":"31","author":"WG Hoover","year":"1985","unstructured":"Hoover WG (1985) Canonical dynamics: equilibrium phase-space distributions. Phys Rev A 31:1695\u20131697. https:\/\/doi.org\/10.1103\/PhysRevA.31.1695","journal-title":"Phys Rev A"},{"key":"6729_CR28","doi-asserted-by":"publisher","first-page":"4177","DOI":"10.1063\/1.467468","volume":"101","author":"GJ Martyna","year":"1994","unstructured":"Martyna GJ, Tobias DJ, Klein ML (1994) Constant pressure molecular dynamics algorithms. J Chem Phys 101:4177\u20134189. https:\/\/doi.org\/10.1063\/1.467468","journal-title":"J Chem Phys"},{"key":"6729_CR29","doi-asserted-by":"crossref","unstructured":"Bowers KJ, Chow DE, Xu H, Dror RO, Eastwood MP, Gregersen BA, Klepeis JL, Kolossvary I, Moraes MA, Sacerdoti FD, Salmon JK, Shan Y, Shaw DE (2006) Scalable algorithms for molecular dynamics simulations on commodity clusters. In: ACM\/IEEE SC 2006 Conference (SC\u201906). IEEE, pp 43\u201343","DOI":"10.1109\/SC.2006.54"},{"key":"6729_CR30","unstructured":"RStudio Team (2015) RStudio: integrated development for R. RStudio, Inc., Boston MU http:\/\/www.rstudio.com\/.RStudio. rstudio. com\/. RStudio"},{"key":"6729_CR31","unstructured":"Schr\u00f6dinger L (2015) The PyMOL molecular graphics system, Version 2.0"},{"key":"6729_CR32","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-75969-2","volume-title":"Lattice","author":"D Sarkar","year":"2008","unstructured":"Sarkar D (2008) Lattice. Springer New York, New York, NY"},{"key":"6729_CR33","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-98141-3","volume-title":"ggplot2","author":"H Wickham","year":"2009","unstructured":"Wickham H (2009) ggplot2. Springer New York, New York, NY"},{"key":"6729_CR34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v021.i12","volume":"21","author":"H Wickham","year":"2007","unstructured":"Wickham H (2007) Reshaping data with the reshape package. J Stat Softw 21:1\u201320. https:\/\/doi.org\/10.18637\/jss.v021.i12","journal-title":"J Stat Softw"},{"key":"6729_CR35","unstructured":"Pinheiro J, Bates D (2025) nlme: linear and nonlinear mixed effects models. CRAN Contrib. Packag"},{"key":"6729_CR36","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/j.1467-9868.2010.00749.x","volume":"73","author":"SN Wood","year":"2011","unstructured":"Wood SN (2011) Fast stable restricted maximum likelihood and marginal likelihood estimation of semiparametric generalized linear models. J R Stat Soc Ser B Stat Methodol 73:3\u201336. https:\/\/doi.org\/10.1111\/j.1467-9868.2010.00749.x","journal-title":"J R Stat Soc Ser B Stat Methodol"},{"key":"6729_CR37","doi-asserted-by":"crossref","unstructured":"Schutten G-J, Chan C, Brohan P, Steuer D, Leeper TJ (2014) readODS: read and write ODS files. CRAN Contrib. Packag","DOI":"10.32614\/CRAN.package.readODS"},{"key":"6729_CR38","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23081899","volume":"23","author":"T Pantsar","year":"2018","unstructured":"Pantsar T, Poso A (2018) Binding affinity via docking: fact and fiction. Molecules 23:1899. https:\/\/doi.org\/10.3390\/molecules23081899","journal-title":"Molecules"}],"container-title":["Journal of Molecular Modeling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00894-026-06729-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00894-026-06729-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00894-026-06729-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T06:15:10Z","timestamp":1778307310000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00894-026-06729-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,27]]},"references-count":38,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["6729"],"URL":"https:\/\/doi.org\/10.1007\/s00894-026-06729-0","relation":{},"ISSN":["1610-2940","0948-5023"],"issn-type":[{"value":"1610-2940","type":"print"},{"value":"0948-5023","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,27]]},"assertion":[{"value":"25 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2026","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":"147"}}