{"paper_id":"369acb34-876b-4c6f-bec4-cd14f2e83422","body_text":"Identification of crucial genes and biological pathways in lung adenocarcinoma by network pharmacology, molecular docking, and simulation studies | 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 Identification of crucial genes and biological pathways in lung adenocarcinoma by network pharmacology, molecular docking, and simulation studies Saba Ehsan, Anupriya Chaudhary, Supriya Maurya, Divya Mishra, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9147467/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 14 You are reading this latest preprint version Abstract Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, largely due to chemoresistance treatment-associated toxicity. This research employed integrated network pharmacology, molecular docking, and molecular dynamics (MD) simulation to investigate the therapeutic potential of bioactive compounds from Pleurotus membranaceus (PM). Four of the 23 bioactive compounds found by literature mining and Swiss ADME-based drug-likeness screening satisfied the criteria for drug-likeness. Using SwissTargetPrediction, SuperPred, PharmMapper, and DIGEP-Pred, 609 possible molecular targets were identified. Cross-referencing with 3,025 LUAD-associated genes from OMIM, DisGeNET, and GeneCards yielded 226 overlapping targets. These targets were further analyzed through Protein-protein interaction (PPI) networks, gene ontology, and pathway enrichment analyses, alongside evaluation of gene expression, overall survival, protein expression, promoter methylation, and immune infiltration profiles. Key hub genes including AKT1, HSP90AA1, IL6, CASP3, and SRC were identified as central regulators of cancer initiation and progression. Molecular docking revealed that AKT1 exhibited the highest binding affinity with Isosorbide (−9.6 kcal/mol). MD simulation confirmed the stability of the AKT1–Isosorbide complex, with a binding free energy of −193.8 kJ/mol. Energy decomposition analysis indicated that complex stabilization was primarily drive by complementarity and hydrophobic interactions. Collectively, these findings suggest that bioactive compounds of Pleurotus membranaceus, particularly isosorbide, hold promising therapeutic potential LUAD by inducing apoptosis, inhibiting angiogenesis, and suppressing metastasis. Future experimental validation is warranted to translate these computational findings into clinical application. Pleurotus membranaceus lung adenocarcinoma network pharmacology molecular docking molecular dynamics simulation Full Text Additional Declarations Competing interest reported. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 13 May, 2026 Reviews received at journal 22 Apr, 2026 Reviews received at journal 18 Apr, 2026 Reviews received at journal 17 Apr, 2026 Reviewers agreed at journal 13 Apr, 2026 Reviewers agreed at journal 13 Apr, 2026 Reviewers agreed at journal 31 Mar, 2026 Reviewers agreed at journal 30 Mar, 2026 Reviewers agreed at journal 25 Mar, 2026 Reviewers invited by journal 25 Mar, 2026 Editor invited by journal 24 Mar, 2026 Editor assigned by journal 20 Mar, 2026 Submission checks completed at journal 20 Mar, 2026 First submitted to journal 17 Mar, 2026 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. 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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-9147467\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":612307210,\"identity\":\"f3d72996-58fa-4a6e-91fc-57434563d194\",\"order_by\":0,\"name\":\"Saba Ehsan\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Allahabad\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Saba\",\"middleName\":\"\",\"lastName\":\"Ehsan\",\"suffix\":\"\"},{\"id\":612307211,\"identity\":\"d8973b76-6e5a-4b0d-a420-c77a0c46568e\",\"order_by\":1,\"name\":\"Anupriya Chaudhary\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Allahabad\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Anupriya\",\"middleName\":\"\",\"lastName\":\"Chaudhary\",\"suffix\":\"\"},{\"id\":612307212,\"identity\":\"e386e45d-ab90-4a94-9ed9-0856fc2e89ae\",\"order_by\":2,\"name\":\"Supriya Maurya\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Allahabad\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Supriya\",\"middleName\":\"\",\"lastName\":\"Maurya\",\"suffix\":\"\"},{\"id\":612307213,\"identity\":\"79103973-1105-4978-b74e-477d7e3ebb09\",\"order_by\":3,\"name\":\"Divya Mishra\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Hadassah Academic College\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Divya\",\"middleName\":\"\",\"lastName\":\"Mishra\",\"suffix\":\"\"},{\"id\":612307214,\"identity\":\"27f4ff06-10b9-499e-9d40-6eb6c197cb3d\",\"order_by\":4,\"name\":\"Mohan P. 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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\",\"formattedTitle\":\"Identification of crucial genes and biological pathways in lung adenocarcinoma by network pharmacology, molecular docking, and simulation studies\",\"fulltext\":[],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":false,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":true,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":true,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"discover-chemistry\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"\",\"sideBox\":\"Learn more about [Discover Chemistry](https://link.springer.com/journal/44371)\",\"snPcode\":\"44371\",\"submissionUrl\":\"https://submission.nature.com/new-submission/44371/3\",\"title\":\"Discover Chemistry\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"stoa\",\"reportingPortfolio\":\"Discover Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Pleurotus membranaceus, lung adenocarcinoma, network pharmacology, molecular docking, molecular dynamics simulation \",\"lastPublishedDoi\":\"10.21203/rs.3.rs-9147467/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-9147467/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003eLung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, largely due to chemoresistance treatment-associated toxicity. This research employed integrated network pharmacology, molecular docking, and molecular dynamics (MD) simulation to investigate the therapeutic potential of bioactive compounds from Pleurotus membranaceus (PM). Four of the 23 bioactive compounds found by literature mining and Swiss ADME-based drug-likeness screening satisfied the criteria for drug-likeness. Using SwissTargetPrediction, SuperPred, PharmMapper, and DIGEP-Pred, 609 possible molecular targets were identified. Cross-referencing with 3,025 LUAD-associated genes from OMIM, DisGeNET, and GeneCards yielded 226 overlapping targets. These targets were further analyzed through Protein-protein interaction (PPI) networks, gene ontology, and pathway enrichment analyses, alongside evaluation of gene expression, overall survival, protein expression, promoter methylation, and immune infiltration profiles. Key hub genes including AKT1, HSP90AA1, IL6, CASP3, and SRC were identified as central regulators of cancer initiation and progression. Molecular docking revealed that AKT1 exhibited the highest binding affinity with Isosorbide (−9.6 kcal/mol). MD simulation confirmed the stability of the AKT1–Isosorbide complex, with a binding free energy of −193.8 kJ/mol. Energy decomposition analysis indicated that complex stabilization was primarily drive by complementarity and hydrophobic interactions. Collectively, these findings suggest that bioactive compounds of Pleurotus membranaceus, particularly isosorbide, hold promising therapeutic potential LUAD by inducing apoptosis, inhibiting angiogenesis, and suppressing metastasis. Future experimental validation is warranted to translate these computational findings into clinical application.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Identification of crucial genes and biological pathways in lung adenocarcinoma by network pharmacology, molecular docking, and simulation studies\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2026-03-26 17:04:45\",\"doi\":\"10.21203/rs.3.rs-9147467/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Revision requested\",\"date\":\"2026-05-13T14:54:01+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2026-04-22T15:35:23+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2026-04-18T18:45:59+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2026-04-17T05:00:46+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"191906597533281910745153481570086368249\",\"date\":\"2026-04-13T15:08:05+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"309715185052483569493811922742669359948\",\"date\":\"2026-04-13T14:39:56+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"308433122766018592395467970247827137069\",\"date\":\"2026-03-31T09:43:04+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"100822238981788345320292709787903681951\",\"date\":\"2026-03-30T09:16:06+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"221249738142184703515336743624949635189\",\"date\":\"2026-03-25T15:58:19+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2026-03-25T07:22:47+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvited\",\"content\":\"\",\"date\":\"2026-03-24T13:51:27+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2026-03-20T13:15:43+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2026-03-20T13:15:40+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"Discover Chemistry\",\"date\":\"2026-03-17T10:08:51+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"discover-chemistry\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"\",\"sideBox\":\"Learn more about [Discover Chemistry](https://link.springer.com/journal/44371)\",\"snPcode\":\"44371\",\"submissionUrl\":\"https://submission.nature.com/new-submission/44371/3\",\"title\":\"Discover Chemistry\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"stoa\",\"reportingPortfolio\":\"Discover Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"b5deafbb-ec4b-4848-aac2-50b9cdeeb2b1\",\"owner\":[],\"postedDate\":\"March 26th, 2026\",\"published\":true,\"recentEditorialEvents\":[{\"type\":\"decision\",\"content\":\"Revision requested\",\"date\":\"2026-05-13T14:54:01+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"in-revision\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2026-05-13T15:24:05+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2026-03-26 17:04:45\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-9147467\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-9147467\",\"identity\":\"rs-9147467\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}