Bridging Quantum Mechanics and Biology at the Million-Atom Scale

Bridging Quantum Mechanics and Biology at the Million-Atom Scale | 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 Physical Sciences - Article Bridging Quantum Mechanics and Biology at the Million-Atom Scale Martin Garcia, Luc Wieners This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7327472/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Apr, 2026 Read the published version in Communications Chemistry → Version 1 posted You are reading this latest preprint version Abstract Quantum-mechanical simulations provide the most fundamental description of matter, yet their computational cost has limited applications to systems containing at most thousands of atoms. Here, we present an all-electron quantum-mechanical framework that extends the accessible system size to the multimillion-atom regime. By combining an algorithmically optimized Hartree-Fock formalism with divide-and-conquer, our new approach efficiently handles structures containing millions of atoms with subatomic resolution. We demonstrate this approach on very large biological systems, including a complete bacteriophage in water, totalling over 150 million electrons, representing, to our knowledge, the largest quantum-mechanical calculation performed to date. Our framework allows computing spectral data for DNA and drugs and enables protein structure assessments in strong agreement with structure evaluations by AlphaFold. This approach opens new avenues in quantum physics, structural biology, spectroscopy, bioinformatics, medicine, and materials science. Physical sciences/Physics/Biological physics Biological sciences/Biophysics/Computational biophysics Biological sciences/Computational biology and bioinformatics/Computational models Physical sciences/Physics/Quantum physics/Quantum simulation Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Published Journal Publication published 29 Apr, 2026 Read the published version in Communications Chemistry → 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. 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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-7327472","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Physical Sciences - Article","associatedPublications":[],"authors":[{"id":509604572,"identity":"0659d554-d3be-4d67-8351-42fc10e074e5","order_by":0,"name":"Martin Garcia","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0003-2418-1902","institution":"Universität Kassel","correspondingAuthor":true,"prefix":"","firstName":"Martin","middleName":"","lastName":"Garcia","suffix":""},{"id":509604573,"identity":"26ce5ab6-6b57-4637-a16c-66396b2c802d","order_by":1,"name":"Luc Wieners","email":"","orcid":"","institution":"University of Kassel","correspondingAuthor":false,"prefix":"","firstName":"Luc","middleName":"","lastName":"Wieners","suffix":""}],"badges":[],"createdAt":"2025-08-08 12:55:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7327472/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7327472/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s42004-026-02038-y","type":"published","date":"2026-04-29T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":108494934,"identity":"dc170ba2-0c2b-4280-a93c-88806f3b8ab0","added_by":"auto","created_at":"2026-05-05 10:08:08","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2871145,"visible":true,"origin":"","legend":"","description":"","filename":"BridgingQuantumMechanicsandBiologyattheMillionAtomScale.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7327472/v1_covered_d83f1d9f-395f-45c1-b2b1-7240a2f1bec9.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Bridging Quantum Mechanics and Biology at the Million-Atom Scale","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7327472/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7327472/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eQuantum-mechanical simulations provide the most fundamental description of matter, yet their computational cost has limited applications to systems containing at most thousands of atoms. 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