Exploring the Electronic Structure of Knotted Proteins: The Case of Two Ornithine Transcarbamylase Family

Exploring the Electronic Structure of Knotted Proteins: The Case of Two Ornithine Transcarbamylase Family | 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 Exploring the Electronic Structure of Knotted Proteins: The Case of Two Ornithine Transcarbamylase Family Jose Cicero Alves Silva, Igor Barden Grillo, Gabriel A. Urquiza-Carvalho, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3914716/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Jul, 2024 Read the published version in Journal of Molecular Modeling → Version 1 posted 4 You are reading this latest preprint version Abstract Geometrical knots are rare structural arrangements in proteins in which the polypeptide chain ties itself into a knot, which is very intriguing due to the uncertainty of their impact on the protein properties. Presently, classical molecular dynamics is the most employed technique in the few studies found on this topic, which means that any information on how the presence of knots affects the reactivity and electronic properties of proteins is even scarcer. Thus, using the new software, PRIMoRDiA, developed by our group to explore the electronic structure of biological macromolecules, we evaluated several local quantum chemical descriptors to unveil relevant patterns potentially originating from the presence of the geometrical knot in two proteins, as a case of study. We compared several sampled structures from two enzymes that are highly similar in both tertiary structure and function, but one of them has a knot whereas the other does not. We found that the same amino-acid residues in the knot core have statistically larger values for the unknotted protein, for both hard-hard and soft-soft interaction descriptors. Additionally, we explored the variation in several reactivity and other quantum chemical properties calculated from a set of snapshot structures of whole proteins. We present a computationally feasible protocol that combines structures sampled from nanoscale molecular dynamics trajectories, semiempirical calculations of the entire protein atom set and the use of our software PRIMoRDiA to compute molecular quantum chemical descriptors. From this protocol we showed that the is possible to separate the contribution of the geometrical knot to the reactivity and other electronic structure properties. Knotted Proteins Quantum Chemical Descriptors Protein Electronic Structure Structural Fluctuations Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 15 Jul, 2024 Read the published version in Journal of Molecular Modeling → Version 1 posted Editorial decision: Revision requested 01 Feb, 2024 Editor assigned by journal 01 Feb, 2024 Submission checks completed at journal 01 Feb, 2024 First submitted to journal 31 Jan, 2024 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-3914716","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":270410175,"identity":"8b305c0b-2fd8-46d9-a4c9-f8d842a989da","order_by":0,"name":"Jose Cicero Alves Silva","email":"","orcid":"","institution":"Federal University of Paraíba","correspondingAuthor":false,"prefix":"","firstName":"Jose","middleName":"Cicero Alves","lastName":"Silva","suffix":""},{"id":270410176,"identity":"9f94418c-8258-40f3-8927-5957a0ca675b","order_by":1,"name":"Igor Barden Grillo","email":"","orcid":"","institution":"Federal University of Paraíba","correspondingAuthor":false,"prefix":"","firstName":"Igor","middleName":"Barden","lastName":"Grillo","suffix":""},{"id":270410177,"identity":"6af2bb12-1bc0-4ffa-b953-f65d1d6718b0","order_by":2,"name":"Gabriel A. Urquiza-Carvalho","email":"","orcid":"","institution":"Federal University of Pernambuco","correspondingAuthor":false,"prefix":"","firstName":"Gabriel","middleName":"A.","lastName":"Urquiza-Carvalho","suffix":""},{"id":270410178,"identity":"34e72f72-f9cf-4646-acb7-e74aba1a49cb","order_by":3,"name":"Gerd Bruno Rocha","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0UlEQVRIiWNgGAWjYDACCQbGByCSDcyzYUgAsglqYTZAaEkjTgsbkhpitMhH9z6reNtmEc3HfvgBM0/CnTwG6d4HeLUY3jludnNum0RuG0+aAVDLs2IGmeMG+LXMSGO7zQvSIsFgwMz743Big0QafoeBtBRDtLB/ANpChBZ5iTQ2ZogWHgPitBjIHGOWnHMO5JecgoNzgH5hkzlGwJbZbYwf3pTV5c5vP77xwRtgiPFLtxGw5QCQ4IFyDoAQG34NQFsakLRAdI2CUTAKRsEoQAMAj6hBAPb8miQAAAAASUVORK5CYII=","orcid":"","institution":"Federal University of Paraíba","correspondingAuthor":true,"prefix":"","firstName":"Gerd","middleName":"Bruno","lastName":"Rocha","suffix":""}],"badges":[],"createdAt":"2024-01-31 18:00:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3914716/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3914716/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00894-024-06009-9","type":"published","date":"2024-07-15T16:05:13+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":61596507,"identity":"2a071195-df06-40d3-8d4d-d9f0733943c1","added_by":"auto","created_at":"2024-08-01 17:28:09","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3792320,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3914716/v1_covered_6f4e03ad-6031-4b64-bcce-7abc58745049.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Exploring the Electronic Structure of Knotted Proteins: The Case of Two Ornithine Transcarbamylase Family","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":"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":"Knotted Proteins, Quantum Chemical Descriptors, Protein Electronic Structure,Structural Fluctuations","lastPublishedDoi":"10.21203/rs.3.rs-3914716/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3914716/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Geometrical knots are rare structural arrangements in proteins in which the polypeptide chain ties itself into a knot, which is very intriguing due to the uncertainty of their impact on the protein properties. Presently, classical molecular dynamics is the most employed technique in the few studies found on this topic, which means that any information on how the presence of knots affects the reactivity and electronic properties of proteins is even scarcer. Thus, using the new software, PRIMoRDiA, developed by our group to explore the electronic structure of biological macromolecules, we evaluated several local quantum chemical descriptors to unveil relevant patterns potentially originating from the presence of the geometrical knot in two proteins, as a case of study. We compared several sampled structures from two enzymes that are highly similar in both tertiary structure and function, but one of them has a knot whereas the other does not. We found that the same amino-acid residues in the knot core have statistically larger values for the unknotted protein, for both hard-hard and soft-soft interaction descriptors. Additionally, we explored the variation in several reactivity and other quantum chemical properties calculated from a set of snapshot structures of whole proteins. We present a computationally feasible protocol that combines structures sampled from nanoscale molecular dynamics trajectories, semiempirical calculations of the entire protein atom set and the use of our software PRIMoRDiA to compute molecular quantum chemical descriptors. From this protocol we showed that the is possible to separate the contribution of the geometrical knot to the reactivity and other electronic structure properties.","manuscriptTitle":"Exploring the Electronic Structure of Knotted Proteins: The Case of Two Ornithine Transcarbamylase Family","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-02 07:09:13","doi":"10.21203/rs.3.rs-3914716/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-02-01T08:26:55+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-02-01T08:26:16+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-02-01T06:40:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Molecular Modeling","date":"2024-01-31T17:39:35+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":"62305327-e011-4bc7-a90c-37b86ae79899","owner":[],"postedDate":"February 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-08-01T17:11:16+00:00","versionOfRecord":{"articleIdentity":"rs-3914716","link":"https://doi.org/10.1007/s00894-024-06009-9","journal":{"identity":"journal-of-molecular-modeling","isVorOnly":false,"title":"Journal of Molecular Modeling"},"publishedOn":"2024-07-15 16:05:13","publishedOnDateReadable":"July 15th, 2024"},"versionCreatedAt":"2024-02-02 07:09:13","video":"","vorDoi":"10.1007/s00894-024-06009-9","vorDoiUrl":"https://doi.org/10.1007/s00894-024-06009-9","workflowStages":[]},"version":"v1","identity":"rs-3914716","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3914716","identity":"rs-3914716","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}