Distinct Binding Mode of BAFF antagonist antibodies Belimumab and Tabalumab, analyzed by computer simulation

Distinct Binding Mode of BAFF antagonist antibodies Belimumab and Tabalumab, analyzed by computer simulation | 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 Distinct Binding Mode of BAFF antagonist antibodies Belimumab and Tabalumab, analyzed by computer simulation Yaxin Jiang, Jian Sun, Jing Wei This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-974192/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract B-cell activating factor (BAFF) can binding to specific receptors and activate signaling pathways associated with B cell activation. Belimumab and tabalumab are anti-BAFF monoclonal antibodies, while belimumab was proved by FDA in 2011 as a targeted therapy for systemic lupus erythematosus (SLE) and showed better clinical effect than tabalumab. The combination modes of BAFF-belimumab complex and BAFF-tabalumab complex were simulated to better understand the reason for the difference of the inhibition effect between belimumab and tabalumab. The structures of belimumab and tabalumab were constructed by homology modeling. The combination mode of BAFF-belimumab complex was analyzed by molecular dynamics simulation, and the combination mode of BAFF-tabalumab complex was analyzed by protein-protein docking after molecular dynamics simulation. Both belimumab and tabalumab contacted with BAFF at the same hydrophobic center which the natural receptors of BAFF bind to. I51, F54, K58 D100, D101, L102, L103, P105 of belimumab heavy chain and R27, Y30, K49, S65 of belimumab light chain contribute to the BAFF-belimumab interaction mainly by hydrogen bond, salt bridge and hydrophobic effect. More important, Belimumab could contact with L83 of BAFF and produced a steric hindrance with the adjacent BAFF trimers, while tabalumab could not. Belimumab had better clinical effect than tabalumab mainly because it could bind to L83 of BAFF and affect the formation of BAFF 60-mer, in addition to inhibition of the interaction of BAFF with its receptors. Chemical Engineering Inorganic Chemistry Organic Chemistry BAFF belimumab tabalumab computation analysis systemic lupus erythematosus Full Text Supplementary Files GraphicalAbstract.tif Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revisions needed 22 Mar, 2022 Reviews received at journal 29 Dec, 2021 Reviewers invited by journal 21 Oct, 2021 Editor invited by journal 15 Oct, 2021 Editor assigned by journal 14 Oct, 2021 First submitted to journal 14 Oct, 2021 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. 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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-974192","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":58243660,"identity":"637ea698-7db6-4ced-aa4d-560fbe91612b","order_by":0,"name":"Yaxin Jiang","email":"","orcid":"","institution":"Tianjin University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yaxin","middleName":"","lastName":"Jiang","suffix":""},{"id":58243661,"identity":"008996e2-f5fd-4ba0-be91-b01d2b3a750b","order_by":1,"name":"Jian Sun","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsUlEQVRIiWNgGAWjYJACgw8MbGCaeC2GMxJI1cLMk8BAghb5GbkHim1/8CU2sDdvk2CouUNYi8GNvATjnAS2xAaeY2USDMeeEaFFIscAokUix0yCseEwMQ4DarEAaZF/Q6QWhhtALQxgW3iI1GJw5o2BYU8am3EbT1qxRcIxYhzWnmNm8MPmmGw/++GNNz7UEOMwBgY2YHwcg8R/AlEagDH5gIGhhki1o2AUjIJRMCIBAOY4Ms/4LaAOAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-1749-6789","institution":"Tianjin University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Jian","middleName":"","lastName":"Sun","suffix":""},{"id":58243662,"identity":"2513d866-64f4-423c-8b30-0c34c8d2df96","order_by":2,"name":"Jing Wei","email":"","orcid":"","institution":"Tianjin University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Wei","suffix":""}],"badges":[],"createdAt":"2021-10-15 23:49:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-974192/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-974192/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":14873433,"identity":"4ca2caf6-9bc2-425f-b71c-766cfbed1143","added_by":"auto","created_at":"2021-10-25 15:32:42","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":761699,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-974192/v1_covered.pdf"},{"id":14873432,"identity":"e55bbc67-7b20-4627-8831-7cef306eaaf0","added_by":"auto","created_at":"2021-10-25 15:32:35","extension":"tif","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":4490740,"visible":true,"origin":"","legend":"","description":"","filename":"GraphicalAbstract.tif","url":"https://assets-eu.researchsquare.com/files/rs-974192/v1/f2ab9184db5392d8148da405.tif"}],"financialInterests":"","formattedTitle":"Distinct Binding Mode of BAFF antagonist antibodies Belimumab and Tabalumab, analyzed by computer simulation","fulltext":[{"header":"Full Text","content":"This preprint is available for \u003ca href='/article/rs-974192/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e."}],"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":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-molecular-modeling","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jmmo","sideBox":"Learn more about [Journal of Molecular Modeling](https://www.springer.com/journal/894)","snPcode":"894","submissionUrl":"https://submission.nature.com/new-submission/894/3","title":"Journal of Molecular Modeling","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"BAFF, belimumab, tabalumab, computation analysis, systemic lupus erythematosus","lastPublishedDoi":"10.21203/rs.3.rs-974192/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-974192/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eB-cell activating factor (BAFF) can binding to specific receptors and activate signaling pathways associated with B cell activation. Belimumab and tabalumab are anti-BAFF monoclonal antibodies, while belimumab was proved by FDA in 2011 as a targeted therapy for systemic lupus erythematosus (SLE) and showed better clinical effect than tabalumab. The combination modes of BAFF-belimumab complex and BAFF-tabalumab complex were simulated to better understand the reason for the difference of the inhibition effect between belimumab and tabalumab. The structures of belimumab and tabalumab were constructed by homology modeling. The combination mode of BAFF-belimumab complex was analyzed by molecular dynamics simulation, and the combination mode of BAFF-tabalumab complex was analyzed by protein-protein docking after molecular dynamics simulation. Both belimumab and tabalumab contacted with BAFF at the same hydrophobic center which the natural receptors of BAFF bind to. I51, F54, K58 D100, D101, L102, L103, P105 of belimumab heavy chain and R27, Y30, K49, S65 of belimumab light chain contribute to the BAFF-belimumab interaction mainly by hydrogen bond, salt bridge and hydrophobic effect. More important, Belimumab could contact with L83 of BAFF and produced a steric hindrance with the adjacent BAFF trimers, while tabalumab could not. Belimumab had better clinical effect than tabalumab mainly because it could bind to L83 of BAFF and affect the formation of BAFF 60-mer, in addition to inhibition of the interaction of BAFF with its receptors.\u003c/p\u003e","manuscriptTitle":"Distinct Binding Mode of BAFF antagonist antibodies Belimumab and Tabalumab, analyzed by computer simulation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-10-25 15:32:33","doi":"10.21203/rs.3.rs-974192/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revisions needed","date":"2022-03-22T20:23:12+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-12-29T10:25:17+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-10-21T17:18:20+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Journal of Molecular Modeling","date":"2021-10-15T07:32:32+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2021-10-15T03:48:57+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Molecular Modeling","date":"2021-10-14T04:18:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-molecular-modeling","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jmmo","sideBox":"Learn more about [Journal of Molecular Modeling](https://www.springer.com/journal/894)","snPcode":"894","submissionUrl":"https://submission.nature.com/new-submission/894/3","title":"Journal of Molecular Modeling","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"709134cf-af62-449f-a273-b94e9361199b","owner":[],"postedDate":"October 25th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":8069952,"name":"Chemical Engineering"},{"id":8069953,"name":"Inorganic Chemistry"},{"id":8069954,"name":"Organic Chemistry"}],"tags":[],"updatedAt":"2022-05-02T22:02:42+00:00","versionOfRecord":[],"versionCreatedAt":"2021-10-25 15:32:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-974192","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-974192","identity":"rs-974192","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}