Discovery of Novel Natural Product-Derived EGFR Inhibitors Using Multiple Linear Regression, Stacked Ensemble Regression, and Fingerprinting Approaches

Discovery of Novel Natural Product-Derived EGFR Inhibitors Using Multiple Linear Regression, Stacked Ensemble Regression, and Fingerprinting Approaches | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Discovery of Novel Natural Product-Derived EGFR Inhibitors Using Multiple Linear Regression, Stacked Ensemble Regression, and Fingerprinting Approaches Said Bitam, Mabrouk Hamadache, Salah Hanini This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7104591/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 13 Dec, 2025 Read the published version in Journal of Computer-Aided Molecular Design → Version 1 posted 7 You are reading this latest preprint version Abstract This study developed and validated Quantitative Structure-Activity Relationship (QSAR) models to predict the inhibitory activity (pIC\textsubscript{50}) of 225 EGFR inhibitors. A genetic algorithm selected eight molecular descriptors, which were used to construct two models: a multiple linear regression (MLR) and a stacked ensemble regression (SER). The Stacked Ensemble Regression (SER) model showed only marginally higher accuracy ( \((\Delta r^{2} = + 0.022)\) ) but exhibited greater instability ( \((\Delta r_{m(test)}^{2})\) = 0.0802 vs. MLR's 0.0184) and reduced interpretability. Thus, MLR was retained as the primary model due to its OECD-compliant mechanistic transparency and superior generalizability. Rigorous applicability domain analysis confirmed the MLR model's reliability. Notably, molecular docking (PDB ID: 8A27) identified a top-ranked inhibitor (Compound 121) with high binding affinity (-12.023 kcal/mol), forming critical hydrogen bonds and hydrophobic interactions with EGFR's active site. Virtual screening of 32 structural analogs of Compound 121 revealed additional promising candidates. This work provides a robust framework for EGFR inhibitor discovery, combining computational modeling with structural insights. EGFR inhibitors QSAR Stacked Ensemble Regression MLR Molecular docking Virtual screening Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryFile.xlsx Cite Share Download PDF Status: Published Journal Publication published 13 Dec, 2025 Read the published version in Journal of Computer-Aided Molecular Design → Version 1 posted Editorial decision: Revision requested 23 Oct, 2025 Reviews received at journal 26 Sep, 2025 Reviewers agreed at journal 16 Sep, 2025 Reviewers invited by journal 14 Sep, 2025 Editor assigned by journal 21 Jul, 2025 Submission checks completed at journal 13 Jul, 2025 First submitted to journal 11 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7104591","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":515892353,"identity":"7332a525-2673-49dd-bf6f-f845548e4c5c","order_by":0,"name":"Said Bitam","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/UlEQVRIiWNgGAWjYBACA2Yog40h+QCQCxEEYmZcOoBamGFa0hKI1IKQyzFACOLTYs7Of/DTDYY6eT72nG/SBQWHGXTbmzc++MFgbY9Li2UzM7N0DsNhwzaet9ukZxgcZjA7c6zYsIchHac1BoeZGYBaDjC2SeRuk+YxSKvfdiPHTIKH4TAbHi3Mv3MY6uzbJHKegbQwmN1/Y/7zD8NhHjxa2IC2MCcCtbABtdgwmN3gMWMG2iKBxy9m1jkGh5PbeJ4ZW4O1nEkrlpYxSDfApcWc/+Dj2zkVdbbz25Mf3ub5I8Fgdvzwxo9vKnCHGNR5RIiMglEwCkbBKCABAABw4Ef58yQRbwAAAABJRU5ErkJggg==","orcid":"","institution":"Laboratory of Biomaterials and Transport Phenomena (LBMPT), University of Médéa","correspondingAuthor":true,"prefix":"","firstName":"Said","middleName":"","lastName":"Bitam","suffix":""},{"id":515892354,"identity":"aec62742-e688-4305-bfef-bb01bb1e3ee3","order_by":1,"name":"Mabrouk Hamadache","email":"","orcid":"","institution":"Laboratory of Biomaterials and Transport Phenomena (LBMPT), University of Médéa","correspondingAuthor":false,"prefix":"","firstName":"Mabrouk","middleName":"","lastName":"Hamadache","suffix":""},{"id":515892355,"identity":"d6278e3a-dd7a-4e0c-be1d-56fb629e4c61","order_by":2,"name":"Salah Hanini","email":"","orcid":"","institution":"Laboratory of Biomaterials and Transport Phenomena (LBMPT), University of Médéa","correspondingAuthor":false,"prefix":"","firstName":"Salah","middleName":"","lastName":"Hanini","suffix":""}],"badges":[],"createdAt":"2025-07-11 21:38:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7104591/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7104591/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10822-025-00731-z","type":"published","date":"2025-12-13T15:59:42+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":91735220,"identity":"38e33a11-c5f9-4cdd-8322-84f60c96fa10","added_by":"auto","created_at":"2025-09-19 17:16:23","extension":"json","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":4730,"visible":true,"origin":"","legend":"","description":"","filename":"29c0ee2831a74a8488d1d8ffd49c6d9b.json","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/566c1dc450e7b70eb1880b7d.json"},{"id":91734623,"identity":"822ee983-af6a-4c7d-b06a-f7ded2f8f96d","added_by":"auto","created_at":"2025-09-19 17:08:23","extension":"xml","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":97473,"visible":true,"origin":"","legend":"","description":"","filename":"29c0ee2831a74a8488d1d8ffd49c6d9b1enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/0c18d68dfc5d3f8969dd5448.xml"},{"id":91734296,"identity":"35b8708e-58eb-461a-b297-70025f66545d","added_by":"auto","created_at":"2025-09-19 17:00:23","extension":"jpg","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":413302,"visible":true,"origin":"","legend":"","description":"","filename":"Fig.1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/1b1926afdc11fb35f2f3a278.jpg"},{"id":91734300,"identity":"889850c8-6fac-48e6-b882-d5bba2f6dcc0","added_by":"auto","created_at":"2025-09-19 17:00:23","extension":"jpg","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":396292,"visible":true,"origin":"","legend":"","description":"","filename":"Fig.2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/904364cd3802a148d222d3c5.jpg"},{"id":91734617,"identity":"86350ab3-0170-492d-a748-786f05cc3869","added_by":"auto","created_at":"2025-09-19 17:08:23","extension":"jpg","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":610312,"visible":true,"origin":"","legend":"","description":"","filename":"Fig.3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/66d48f5022abdd3cdefec686.jpg"},{"id":91734618,"identity":"dc3cf310-34e9-46eb-9aa9-fd1b1048bf23","added_by":"auto","created_at":"2025-09-19 17:08:23","extension":"jpg","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1280814,"visible":true,"origin":"","legend":"","description":"","filename":"Fig.4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/582d08303307d3f9caa558d3.jpg"},{"id":91734298,"identity":"1d7bc4e7-fd4c-4e62-8662-b6e332d25570","added_by":"auto","created_at":"2025-09-19 17:00:23","extension":"jpg","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1160817,"visible":true,"origin":"","legend":"","description":"","filename":"Fig.5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/e15e606d4bd07889a75a1261.jpg"},{"id":91734302,"identity":"bdbe44c6-00cd-48dc-9c89-82c54eb947d5","added_by":"auto","created_at":"2025-09-19 17:00:23","extension":"jpg","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":525782,"visible":true,"origin":"","legend":"","description":"","filename":"Fig.6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/5019ce672940b9d2869d5115.jpg"},{"id":91734626,"identity":"5bf98761-fb54-4b02-af6e-4c86d288d885","added_by":"auto","created_at":"2025-09-19 17:08:23","extension":"pdf","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":4790777,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/68966ef0186975e8a5480dfb.pdf"},{"id":91734314,"identity":"6ff1ce41-095f-4dfc-9aa4-1f7144f64957","added_by":"auto","created_at":"2025-09-19 17:00:23","extension":"xlsx","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2860821,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFile.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/e1728674989e3102b8aee843.xlsx"},{"id":91734310,"identity":"51f9c29e-2a6c-4877-b8aa-f4b01f56f5f2","added_by":"auto","created_at":"2025-09-19 17:00:23","extension":"bst","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":146013,"visible":true,"origin":"","legend":"","description":"","filename":"snapacite.bst","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/1f9d7fd95cda4d0b5b2ef2c4.bst"},{"id":91734621,"identity":"63c21ce2-1f80-48b1-bea5-e088d7f0fc12","added_by":"auto","created_at":"2025-09-19 17:08:23","extension":"bst","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":29828,"visible":true,"origin":"","legend":"","description":"","filename":"snaps.bst","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/6b7e60980e5006fad0970606.bst"},{"id":91734624,"identity":"e28bfcd0-daf3-447f-bd92-ff821acf3b43","added_by":"auto","created_at":"2025-09-19 17:08:23","extension":"bst","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":35515,"visible":true,"origin":"","legend":"","description":"","filename":"snbasic.bst","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/3458a6713524506dc3e64ce0.bst"},{"id":91735221,"identity":"c126172f-acbc-467d-b05e-f0c008fd7ed1","added_by":"auto","created_at":"2025-09-19 17:16:23","extension":"bst","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":33968,"visible":true,"origin":"","legend":"","description":"","filename":"snchicago.bst","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/9f669757c57982ec96b6feab.bst"},{"id":91734305,"identity":"0c21fc70-eca7-4234-b4d7-67841537a298","added_by":"auto","created_at":"2025-09-19 17:00:23","extension":"cls","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":55857,"visible":true,"origin":"","legend":"","description":"","filename":"snjnl.cls","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/1a7fbef89a3e62e3661f9319.cls"},{"id":91734307,"identity":"ed9c4619-97e8-43ce-9894-d93bdb7f250c","added_by":"auto","created_at":"2025-09-19 17:00:23","extension":"bst","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":64023,"visible":true,"origin":"","legend":"","description":"","filename":"snmathphysay.bst","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/b3ddd157a0b7f43a9ee50a39.bst"},{"id":91734625,"identity":"f6949031-c896-452d-a4e7-8b90bea1ff88","added_by":"auto","created_at":"2025-09-19 17:08:23","extension":"bst","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":64166,"visible":true,"origin":"","legend":"","description":"","filename":"snmathphysnum.bst","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/1d1cf1138132efe2fc8e4dc3.bst"},{"id":91734315,"identity":"0a4b7b6d-8190-4343-a236-03796b199f3b","added_by":"auto","created_at":"2025-09-19 17:00:23","extension":"bst","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":37333,"visible":true,"origin":"","legend":"","description":"","filename":"snnature.bst","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/bf1024b8ce572717387c58f1.bst"},{"id":91734309,"identity":"a0d2cc70-37bc-4475-8992-32a365de9a98","added_by":"auto","created_at":"2025-09-19 17:00:23","extension":"bst","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":39951,"visible":true,"origin":"","legend":"","description":"","filename":"snvancouveray.bst","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/81b585a5500b5a33bf36917e.bst"},{"id":91734313,"identity":"d08f0e26-d9f0-4cca-9644-2596bb418ca0","added_by":"auto","created_at":"2025-09-19 17:00:23","extension":"bst","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":40758,"visible":true,"origin":"","legend":"","description":"","filename":"snvancouvernum.bst","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/989a88620dfd0c289ce4fb0c.bst"},{"id":91734319,"identity":"1f58f461-e8c1-4103-b167-b0f756d88a30","added_by":"auto","created_at":"2025-09-19 17:00:23","extension":"pdf","order_by":20,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":418495,"visible":true,"origin":"","legend":"","description":"","filename":"usermanual.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/e60c247fce80c157c2d797c7.pdf"},{"id":91735222,"identity":"a52d7105-414b-4a9e-b15e-caea6e60e0bd","added_by":"auto","created_at":"2025-09-19 17:16:23","extension":"xml","order_by":27,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":107499,"visible":true,"origin":"","legend":"","description":"","filename":"29c0ee2831a74a8488d1d8ffd49c6d9b1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/d2b54c4b8aee24c96d9ddbcd.xml"},{"id":91734311,"identity":"2bc01377-240b-422a-aa7a-8437e7594344","added_by":"auto","created_at":"2025-09-19 17:00:23","extension":"html","order_by":28,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":117673,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/19a70caf69b33a0293830c13.html"},{"id":98244781,"identity":"5abd864c-310f-4f99-a6d4-ab4ac34fe668","added_by":"auto","created_at":"2025-12-15 16:15:08","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4760919,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1_covered_0b634448-5d00-4c19-b353-699eef6d8765.pdf"},{"id":91735757,"identity":"83039bb1-bf28-49af-87cb-ab5f1f6023ae","added_by":"auto","created_at":"2025-09-19 17:24:23","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":2860821,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFile.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7104591/v1/0015f226a88b2d923bec2d07.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Discovery of Novel Natural Product-Derived EGFR Inhibitors Using Multiple Linear Regression, Stacked Ensemble Regression, and Fingerprinting Approaches","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-computer-aided-molecular-design","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jcam","sideBox":"Learn more about [Journal of Computer-Aided Molecular Design](http://link.springer.com/journal/10822)","snPcode":"10822","submissionUrl":"https://submission.nature.com/new-submission/10822/3","title":"Journal of Computer-Aided Molecular Design","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"EGFR inhibitors, QSAR, Stacked Ensemble Regression, MLR, Molecular docking, Virtual screening","lastPublishedDoi":"10.21203/rs.3.rs-7104591/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7104591/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study developed and validated Quantitative Structure-Activity Relationship (QSAR) models to predict the inhibitory activity (pIC\\textsubscript{50}) of 225 EGFR inhibitors. A genetic algorithm selected eight molecular descriptors, which were used to construct two models: a multiple linear regression (MLR) and a stacked ensemble regression (SER). The Stacked Ensemble Regression (SER) model showed only marginally higher accuracy (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\((\\Delta r^{2} = + 0.022)\\)\u003c/span\u003e\u003c/span\u003e) but exhibited greater instability (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\((\\Delta r_{m(test)}^{2})\\)\u003c/span\u003e\u003c/span\u003e= 0.0802 vs. MLR's 0.0184) and reduced interpretability. Thus, MLR was retained as the primary model due to its OECD-compliant mechanistic transparency and superior generalizability. Rigorous applicability domain analysis confirmed the MLR model's reliability. Notably, molecular docking (PDB ID: 8A27) identified a top-ranked inhibitor (Compound 121) with high binding affinity (-12.023 kcal/mol), forming critical hydrogen bonds and hydrophobic interactions with EGFR's active site. Virtual screening of 32 structural analogs of Compound 121 revealed additional promising candidates. This work provides a robust framework for EGFR inhibitor discovery, combining computational modeling with structural insights.\u003c/p\u003e","manuscriptTitle":"Discovery of Novel Natural Product-Derived EGFR Inhibitors Using Multiple Linear Regression, Stacked Ensemble Regression, and Fingerprinting Approaches","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-19 17:00:18","doi":"10.21203/rs.3.rs-7104591/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-23T05:12:17+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-26T21:19:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"325103226717492555973466083211114604247","date":"2025-09-16T10:58:25+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-14T10:49:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-21T12:46:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-14T02:08:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Computer-Aided Molecular Design","date":"2025-07-11T21:32:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-computer-aided-molecular-design","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jcam","sideBox":"Learn more about [Journal of Computer-Aided Molecular Design](http://link.springer.com/journal/10822)","snPcode":"10822","submissionUrl":"https://submission.nature.com/new-submission/10822/3","title":"Journal of Computer-Aided Molecular Design","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"3c98c652-d521-41f2-ad72-4dab28fd44d3","owner":[],"postedDate":"September 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-15T16:09:50+00:00","versionOfRecord":{"articleIdentity":"rs-7104591","link":"https://doi.org/10.1007/s10822-025-00731-z","journal":{"identity":"journal-of-computer-aided-molecular-design","isVorOnly":false,"title":"Journal of Computer-Aided Molecular Design"},"publishedOn":"2025-12-13 15:59:42","publishedOnDateReadable":"December 13th, 2025"},"versionCreatedAt":"2025-09-19 17:00:18","video":"","vorDoi":"10.1007/s10822-025-00731-z","vorDoiUrl":"https://doi.org/10.1007/s10822-025-00731-z","workflowStages":[]},"version":"v1","identity":"rs-7104591","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7104591","identity":"rs-7104591","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}