Systematic screening of brain neurotransmitter enzymes for radical pair mechanism competence identifies candidates for magnetic field sensitivity

Systematic screening of brain neurotransmitter enzymes for radical pair mechanism competence reveals quantitative constraints on magnetic field sensitivity | 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 Systematic screening of brain neurotransmitter enzymes for radical pair mechanism competence reveals quantitative constraints on magnetic field sensitivity Hikaru Wakaura This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9278975/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract The radical pair mechanism (RPM) is experimentally validated in avian magnetoreception via cryptochrome, but whether RPM-competent sites exist more broadly among brain enzymes remains unknown. Here we screen nine phosphorus-containing human brain proteins computationally, assigning cofactor-specific $^{31}$P hyperfine coupling constants, and find that eight satisfy all seven necessary conditions for RPM operation under physiological conditions (50~\si{\micro\tesla}, 310~K). The dominant discriminant is the $^{31}$P nuclear spin coherence time, which scales as the sixth power of the electron--phosphorus distance, creating a 64-fold gap between FAD enzymes (160~\si{\micro\second}) and PLP enzymes (2.5~\si{\micro\second}). We identify a complementary trade-off: enzymes with strong hyperfine coupling exhibit fast singlet--triplet mixing but short electron coherence, and vice versa. Density matrix simulation predicts an upper-bound magnetic field effect of $-4.4\%$ on the singlet yield of MAO-A-catalysed serotonin oxidation, assuming zero exchange coupling; the actual magnitude could be negligible if the radical pair separation is small. These findings identify neurotransmitter metabolism as a candidate arena for biological magnetic field effects, but simultaneously reveal that the exchange coupling constraint ($|J| < 10$~MHz required), homeostatic attenuation (7-fold), and CASSCF evidence against SET in MAO-A collectively impose severe quantitative barriers. The primary contribution is a falsifiable framework with experimentally testable predictions, not a claim that RPM operates in these enzymes. Biophysics quantum chemistry quantum information Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions 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-9278975","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":618041232,"identity":"8032db1e-00e2-4846-ba9e-14bc46c5714a","order_by":0,"name":"Hikaru Wakaura","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYBACAyBmbACx2BsMwCJ87BBRIrTwHDAA89mYidYikYDQgheYM/AYfpxRcziff+bjjQ8+7vgjB9JSXIBHi2UDj7HkhmOHLWfcTis2nHnGwBikxXgGPocd4N0g+YDtsAHD7Rwzad42g8Q2kBYe/Fo2/3zw77CB/M0z5r//thnUE6Nlm+TGtsMGBjd4zJgZ2wwS2AhqOcz/zXJmX7qB4Zm0YsneM8aGbcyMDfj9crwt+WbPN2sDueOHN374uUNOnp+9+ZgxvhBjQIkFSAwxthnj04EKIFoYmB8Tr2UUjIJRMApGAAAApB1Ji9H0SDIAAAAASUVORK5CYII=","orcid":"","institution":"QIRI (Quantum Integrated Research Institute Inc.)","correspondingAuthor":true,"prefix":"","firstName":"Hikaru","middleName":"","lastName":"Wakaura","suffix":""}],"badges":[],"createdAt":"2026-03-31 11:22:26","currentVersionCode":2,"declarations":{"humanSubjects":false,"vertebrateSubjects":true,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":true},"doi":"10.21203/rs.3.rs-9278975/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-9278975/v2","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107707818,"identity":"da7b2bb0-918c-45a7-8743-5083861f9500","added_by":"auto","created_at":"2026-04-24 09:21:11","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":382445,"visible":true,"origin":"","legend":"","description":"","filename":"main.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9278975/v2_covered_b4827441-7e90-4b5d-a055-1cc67e4e90a3.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eSystematic screening of brain neurotransmitter enzymes for radical pair mechanism competence reveals quantitative constraints on magnetic field sensitivity\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"QIRI (Quantum Integrated Research Institute Inc.)","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"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":"quantum chemistry, quantum information","lastPublishedDoi":"10.21203/rs.3.rs-9278975/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9278975/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe radical pair mechanism (RPM) is experimentally validated in avian magnetoreception via cryptochrome, but whether RPM-competent sites exist more broadly among brain enzymes remains unknown. Here we screen nine phosphorus-containing human brain proteins computationally, assigning cofactor-specific $^{31}$P hyperfine coupling constants, and find that eight satisfy all seven necessary conditions for RPM operation under physiological conditions (50~\\si{\\micro\\tesla}, 310~K). The dominant discriminant is the $^{31}$P nuclear spin coherence time, which scales as the sixth power of the electron--phosphorus distance, creating a 64-fold gap between FAD enzymes (160~\\si{\\micro\\second}) and PLP enzymes (2.5~\\si{\\micro\\second}). We identify a complementary trade-off: enzymes with strong hyperfine coupling exhibit fast singlet--triplet mixing but short electron coherence, and vice versa. Density matrix simulation predicts an upper-bound magnetic field effect of $-4.4\\%$ on the singlet yield of MAO-A-catalysed serotonin oxidation, assuming zero exchange coupling; the actual magnitude could be negligible if the radical pair separation is small. These findings identify neurotransmitter metabolism as a candidate arena for biological magnetic field effects, but simultaneously reveal that the exchange coupling constraint ($|J| \u0026lt; 10$~MHz required), homeostatic attenuation (7-fold), and CASSCF evidence against SET in MAO-A collectively impose severe quantitative barriers. The primary contribution is a falsifiable framework with experimentally testable predictions, not a claim that RPM operates in these enzymes.\u003c/p\u003e","manuscriptTitle":"Systematic screening of brain neurotransmitter enzymes for radical pair mechanism competence reveals quantitative constraints on magnetic field sensitivity","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2026-04-23 18:49:30","doi":"10.21203/rs.3.rs-9278975/v2","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}},{"code":1,"date":"2026-04-06 06:26:19","doi":"10.21203/rs.3.rs-9278975/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":"8768b55e-2e21-42ac-8c08-24534da08dc1","owner":[],"postedDate":"April 23rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":65938005,"name":"Biophysics"}],"tags":[],"updatedAt":"2026-04-06T06:26:19+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-23 18:49:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-9278975","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9278975","identity":"rs-9278975","version":["v2"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}