Metadynamics and Free-Energy Landscape Approaches for Structural Characterization of Galectin-3

Metadynamics and Free-Energy Landscape Approaches for Structural Characterization of Galectin-3 | 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 Metadynamics and Free-Energy Landscape Approaches for Structural Characterization of Galectin-3 Rik Ganguly, Vladimir N. Uversky, Prosperwell Ingty, Angneh Ngoruh, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4604896/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 The study addresses the three-dimensional structure and folding dynamics of Galectin-3 through the use of in-silico techniques like as DeepMind's AlphaFold, homology modelling, and ab-initio methods. The structural validation of the modelled structures highly supports the AlphaFold model. The N-terminal intrinsically disordered region a particular phenomenon frequently connected to the intrinsically disordered sections of proteins and its unexplored role in liquid-liquid phase separation are highlighted. The protein's metastable states were investigated using free energy landscaping, and the metastable state with the lowest global energy minima was the focus of in-depth dynamics studies. This gave researchers a thorough understanding of the structural flexibility of the Galectin-3 protein and the main factors influencing its coordinated movements. GoldScore and ChemScore are the best scoring functions, according to enrichment analysis, for determining candidate Galectin-3 carbohydrate-binding activity inhibitors. The FDA-approved compound ceftaroline shows high affinity and favourable interactions with the refined complete structure of Galectin-3, according to a newly introduced weighted scoring function that takes into account both GoldScore and ChemScore metrics. Ceftaroline was subjected to 100 ns molecular dynamic (MD) simulations, and the ceftaroline-Galectin-3 complex was found to be stable. This computational work sheds light on the structural dynamics of galectin-3 and lays the groundwork for upcoming experimental confirmations and medical advancements. Galectin-3 AlphaFold homology modelling ab-initio Free energy landscaping 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. 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-4604896","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":321436373,"identity":"c285c0d1-2132-45f6-b0b6-cd9f73a2bbd7","order_by":0,"name":"Rik Ganguly","email":"","orcid":"","institution":"North-Eastern Hill University","correspondingAuthor":false,"prefix":"","firstName":"Rik","middleName":"","lastName":"Ganguly","suffix":""},{"id":321436375,"identity":"2bf6074f-24a0-4165-a50e-54b6089fea51","order_by":1,"name":"Vladimir N. Uversky","email":"","orcid":"","institution":"University of South Florida","correspondingAuthor":false,"prefix":"","firstName":"Vladimir","middleName":"N.","lastName":"Uversky","suffix":""},{"id":321436377,"identity":"bcb28a83-63ad-425c-8919-16fb56d956a3","order_by":2,"name":"Prosperwell Ingty","email":"","orcid":"","institution":"North-Eastern Hill University","correspondingAuthor":false,"prefix":"","firstName":"Prosperwell","middleName":"","lastName":"Ingty","suffix":""},{"id":321436380,"identity":"a16fca01-ef5d-4066-8233-3e0d98a01067","order_by":3,"name":"Angneh Ngoruh","email":"","orcid":"","institution":"North-Eastern Hill University","correspondingAuthor":false,"prefix":"","firstName":"Angneh","middleName":"","lastName":"Ngoruh","suffix":""},{"id":321436381,"identity":"162c16bd-eba7-4125-b000-b1f91a47cdbd","order_by":4,"name":"Shashi Kumar Yadav","email":"","orcid":"","institution":"North-Eastern Hill University","correspondingAuthor":false,"prefix":"","firstName":"Shashi","middleName":"Kumar","lastName":"Yadav","suffix":""},{"id":321436382,"identity":"b5868e4b-64fc-49d1-bcbb-36c4c7cdea74","order_by":5,"name":"Rajat Roy","email":"","orcid":"","institution":"North-Eastern Hill University","correspondingAuthor":false,"prefix":"","firstName":"Rajat","middleName":"","lastName":"Roy","suffix":""},{"id":321436383,"identity":"7c2d13c3-ecd5-48a3-9e07-3af18f347f54","order_by":6,"name":"Atanu Bhattacharjee","email":"data:image/png;base64,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","orcid":"","institution":"North-Eastern Hill University","correspondingAuthor":true,"prefix":"","firstName":"Atanu","middleName":"","lastName":"Bhattacharjee","suffix":""}],"badges":[],"createdAt":"2024-06-19 09:42:00","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4604896/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4604896/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":62085391,"identity":"6518a154-00e5-416b-94e6-d3eb7d2eefcd","added_by":"auto","created_at":"2024-08-09 06:37:25","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2160506,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4604896/v1_covered_09b3d6cb-4835-41a2-b623-4cddf2be0468.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Metadynamics and Free-Energy Landscape Approaches for Structural Characterization of Galectin-3","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":"Galectin-3, AlphaFold, homology modelling, ab-initio, Free energy landscaping","lastPublishedDoi":"10.21203/rs.3.rs-4604896/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4604896/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe study addresses the three-dimensional structure and folding dynamics of Galectin-3 through the use of in-silico techniques like as DeepMind's AlphaFold, homology modelling, and ab-initio methods. The structural validation of the modelled structures highly supports the AlphaFold model. The N-terminal intrinsically disordered region a particular phenomenon frequently connected to the intrinsically disordered sections of proteins and its unexplored role in liquid-liquid phase separation are highlighted. The protein's metastable states were investigated using free energy landscaping, and the metastable state with the lowest global energy minima was the focus of in-depth dynamics studies. This gave researchers a thorough understanding of the structural flexibility of the Galectin-3 protein and the main factors influencing its coordinated movements. GoldScore and ChemScore are the best scoring functions, according to enrichment analysis, for determining candidate Galectin-3 carbohydrate-binding activity inhibitors. The FDA-approved compound ceftaroline shows high affinity and favourable interactions with the refined complete structure of Galectin-3, according to a newly introduced weighted scoring function that takes into account both GoldScore and ChemScore metrics. Ceftaroline was subjected to 100 ns molecular dynamic (MD) simulations, and the ceftaroline-Galectin-3 complex was found to be stable. This computational work sheds light on the structural dynamics of galectin-3 and lays the groundwork for upcoming experimental confirmations and medical advancements.\u003c/p\u003e","manuscriptTitle":"Metadynamics and Free-Energy Landscape Approaches for Structural Characterization of Galectin-3","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-10 01:18:50","doi":"10.21203/rs.3.rs-4604896/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","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}}],"origin":"","ownerIdentity":"94c4c465-dcb6-40ee-abea-f63e5d5cdd98","owner":[],"postedDate":"July 10th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-09T06:29:17+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-10 01:18:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4604896","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4604896","identity":"rs-4604896","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}