Uncovering Sequence Effects in Titanium Binding peptides adsorption on TiO2: A Molecular Dynamics Study

Uncovering Sequence Effects in Titanium Binding peptides adsorption on TiO2: A Molecular Dynamics Study | 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 Uncovering Sequence Effects in Titanium Binding peptides adsorption on TiO 2 : A Molecular Dynamics Study Roja Rahmani, Alexander Lyubartsev This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6594907/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Jul, 2025 Read the published version in Scientific Reports → Version 1 posted 11 You are reading this latest preprint version Abstract Titanium binding peptides are useful tools for material functionalization in both biomedical and nanotechnology applications because of their ability to attach selectively to titanium surfaces. In this work, we investigate the adsorption behavior of a series of 360 six amino acids long peptides obtained by permutations of titanium binding peptide residues, RKLPDA, on hydroxylated anatase TiO \(_2\) (101) surfaces using extensive atomistic molecular dynamics (MD) simulations, with the purpose identifying sequences with stronger adsorption affinity to titanium. Our results show that small changes in amino acid order can significantly affect both binding strength and structural conformations. Peptides with arginine at the N-terminus and lysine or aspartic acid near the C-terminus tended to exhibit more stable adsorption. The clustering and radial distribution function (RDF) analyzes revealed different binding modes and key atomic interactions, with nitrogen-containing groups and, in some cases, Na \(^{+}\) ions playing a significant role in the anchoring of peptides to the surface. These findings suggest a detailed sequence-level understanding of peptide-TiO \(_{2}\) interactions and can guide the design of improved peptides for titanium functionalization. Physical sciences/Chemistry/Theoretical chemistry/Computational chemistry Physical sciences/Chemistry/Theoretical chemistry/Molecular dynamics Physical sciences/Materials science/Theory and computation/Atomistic models Physical sciences/Nanoscience and technology/Nanoscale materials/Organic inorganic nanostructures Titanium dioxide peptides adsorption molecular dynamics Full Text Additional Declarations No competing interests reported. Supplementary Files RojaPeptideMDSI.pdf Cite Share Download PDF Status: Published Journal Publication published 24 Jul, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 18 Jun, 2025 Reviews received at journal 17 Jun, 2025 Reviews received at journal 16 Jun, 2025 Reviewers agreed at journal 16 Jun, 2025 Reviewers agreed at journal 19 May, 2025 Reviewers agreed at journal 19 May, 2025 Reviewers invited by journal 19 May, 2025 Editor assigned by journal 19 May, 2025 Editor invited by journal 19 May, 2025 Submission checks completed at journal 16 May, 2025 First submitted to journal 05 May, 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-6594907","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":458523858,"identity":"a50f34f1-4658-46ff-a85c-dcba3782f530","order_by":0,"name":"Roja Rahmani","email":"","orcid":"","institution":"Stockholm University","correspondingAuthor":false,"prefix":"","firstName":"Roja","middleName":"","lastName":"Rahmani","suffix":""},{"id":458523859,"identity":"3d26f6e4-9219-4276-9e42-3bab2367aaef","order_by":1,"name":"Alexander Lyubartsev","email":"data:image/png;base64,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","orcid":"","institution":"Stockholm University","correspondingAuthor":true,"prefix":"","firstName":"Alexander","middleName":"","lastName":"Lyubartsev","suffix":""}],"badges":[],"createdAt":"2025-05-05 13:38:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6594907/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6594907/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-10966-3","type":"published","date":"2025-07-24T15:57:20+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":87757058,"identity":"0e534449-483a-4217-87c5-698ea36ad94c","added_by":"auto","created_at":"2025-07-28 16:10:30","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":6743476,"visible":true,"origin":"","legend":"","description":"","filename":"Submitted.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6594907/v1_covered_28384f7d-8e85-4531-b754-1c678e8fe0fd.pdf"},{"id":83352959,"identity":"2e92b050-e4d4-48d8-98ab-4d62b090fa0d","added_by":"auto","created_at":"2025-05-23 14:24:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":8808076,"visible":true,"origin":"","legend":"","description":"","filename":"RojaPeptideMDSI.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6594907/v1/ddaf46cca2dfb18674c51b49.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eUncovering Sequence Effects in Titanium Binding peptides adsorption on TiO\u003csub\u003e2\u003c/sub\u003e: A Molecular Dynamics Study\u003c/p\u003e","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":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Titanium dioxide, peptides, adsorption, molecular dynamics","lastPublishedDoi":"10.21203/rs.3.rs-6594907/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6594907/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eTitanium binding peptides are useful tools for material functionalization in both biomedical and nanotechnology applications because of their ability to attach selectively to titanium surfaces. In this work, we investigate the adsorption behavior of a series of 360 six amino acids long peptides obtained by permutations of titanium binding peptide residues, RKLPDA, on hydroxylated anatase TiO\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(_2\\)\u003c/span\u003e\u003c/span\u003e (101) surfaces using extensive atomistic molecular dynamics (MD) simulations, with the purpose identifying sequences with stronger adsorption affinity to titanium. Our results show that small changes in amino acid order can significantly affect both binding strength and structural conformations. Peptides with arginine at the N-terminus and lysine or aspartic acid near the C-terminus tended to exhibit more stable adsorption. The clustering and radial distribution function (RDF) analyzes revealed different binding modes and key atomic interactions, with nitrogen-containing groups and, in some cases, Na\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(^{+}\\)\u003c/span\u003e\u003c/span\u003e ions playing a significant role in the anchoring of peptides to the surface. These findings suggest a detailed sequence-level understanding of peptide-TiO\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(_{2}\\)\u003c/span\u003e\u003c/span\u003e interactions and can guide the design of improved peptides for titanium functionalization.\u003c/p\u003e","manuscriptTitle":"Uncovering Sequence Effects in Titanium Binding peptides adsorption on TiO2: A Molecular Dynamics Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-23 14:24:29","doi":"10.21203/rs.3.rs-6594907/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-18T08:23:23+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-17T09:22:54+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-16T15:06:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"37672706007529287813166015796227759998","date":"2025-06-16T14:20:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"236971109667829710636698396362425712332","date":"2025-05-19T07:32:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"179860720076341569536912904578311152820","date":"2025-05-19T07:17:20+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-19T04:22:15+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-19T04:14:23+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-05-19T04:09:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-16T05:15:12+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-05-05T13:22:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2aa96a7b-dbfd-43af-95f8-026892b24356","owner":[],"postedDate":"May 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":48780641,"name":"Physical sciences/Chemistry/Theoretical chemistry/Computational chemistry"},{"id":48780642,"name":"Physical sciences/Chemistry/Theoretical chemistry/Molecular dynamics"},{"id":48780643,"name":"Physical sciences/Materials science/Theory and computation/Atomistic models"},{"id":48780644,"name":"Physical sciences/Nanoscience and technology/Nanoscale materials/Organic inorganic nanostructures"}],"tags":[],"updatedAt":"2025-07-28T16:07:21+00:00","versionOfRecord":{"articleIdentity":"rs-6594907","link":"https://doi.org/10.1038/s41598-025-10966-3","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-07-24 15:57:20","publishedOnDateReadable":"July 24th, 2025"},"versionCreatedAt":"2025-05-23 14:24:29","video":"","vorDoi":"10.1038/s41598-025-10966-3","vorDoiUrl":"https://doi.org/10.1038/s41598-025-10966-3","workflowStages":[]},"version":"v1","identity":"rs-6594907","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6594907","identity":"rs-6594907","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}