Allosteric Regulation of Ectopically Expressed Olfactory Receptors in Tumor Cells: Ligand-Receptor Topology and Deep Learning-Assisted Drug Discovery

Allosteric Regulation of Ectopically Expressed Olfactory Receptors in Tumor Cells: Ligand-Receptor Topology and Deep Learning-Assisted Drug Discovery | 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 Article Allosteric Regulation of Ectopically Expressed Olfactory Receptors in Tumor Cells: Ligand-Receptor Topology and Deep Learning-Assisted Drug Discovery Shivansh Bansal, Saanvi Gudisay This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6950845/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract This research expands existing Olfactory Receptor (ORs) studies, exploring their potential in cancer drug therapy andestablishing a novel pipeline applicable to similar G protein-coupled receptors. Many ORs have been identified across ninecancer types and roughly 1000 cancer cell lines; their activation or inhibition of certain pathways can induce cancer celldeath and reduce proliferation/migration. Our initial focus was OR51E2, utilizing known ligands that modulate the receptor.Approximately 1.4M candidate molecules were sourced from the ZINC20 database based on molecular weight and refinedthrough Schrödinger Maestro’s multi-step virtual screening—including High-Throughput Virtual Screening, standard precision, and extra precision docking—to minimize Gibbs Free Energy upon binding. Compounds with the highest binding affinityunderwent descriptor analysis via Mordred, generating roughly 1,800 molecular descriptors each. Various classification modelswere then trained and tested on bioassay data from EMBL and DUD-E to predict ligand bioactivity. Predictions were finalizedthrough fine-tuning a Support Vector Machine and projecting molecular descriptors in 3D chemical space to improve accuracy.SwissADME assessed ADMET profiles for four promising candidates for OR51E2, each exhibiting drug-like characteristicsacross five metrics, with predicted bioactivity >85%. This study identifies ORs as promising cancer therapy targets, alongsideintroducing a novel drug discovery methodology. Biological sciences/Computational biology and bioinformatics/Computational models Biological sciences/Computational biology and bioinformatics/Data processing Biological sciences/Computational biology and bioinformatics/Databases Biological sciences/Computational biology and bioinformatics/High throughput screening Biological sciences/Computational biology and bioinformatics/Machine learning Biological sciences/Computational biology and bioinformatics/Virtual drug screening Biological sciences/Drug discovery Biological sciences/Drug discovery/Drug screening Biological sciences/Drug discovery/Pharmacology Biological sciences/Drug discovery/Target identification Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. 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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-6950845","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":485367913,"identity":"b52a6882-8e92-4dc3-a240-269afeedc455","order_by":0,"name":"Shivansh Bansal","email":"data:image/png;base64,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","orcid":"","institution":"Dublin High School","correspondingAuthor":true,"prefix":"","firstName":"Shivansh","middleName":"","lastName":"Bansal","suffix":""},{"id":485367916,"identity":"2c508c63-cb40-4508-bb7f-5e97b7835b7a","order_by":1,"name":"Saanvi Gudisay","email":"","orcid":"","institution":"Dublin High School","correspondingAuthor":false,"prefix":"","firstName":"Saanvi","middleName":"","lastName":"Gudisay","suffix":""}],"badges":[],"createdAt":"2025-06-22 17:38:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6950845/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6950845/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87478825,"identity":"dc735d8a-dd7e-4a12-81fa-a3d81f1410ef","added_by":"auto","created_at":"2025-07-24 09:32:15","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2924524,"visible":true,"origin":"","legend":"","description":"","filename":"NatureSubmission1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6950845/v1_covered_7e7d8a0a-3b46-4f28-b5c2-8384985a70b0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Allosteric Regulation of Ectopically Expressed Olfactory Receptors in Tumor Cells: Ligand-Receptor Topology and Deep Learning-Assisted Drug Discovery","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6950845/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6950845/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"This research expands existing Olfactory Receptor (ORs) studies, exploring their potential in cancer drug therapy andestablishing a novel pipeline applicable to similar G protein-coupled receptors. 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