Emergence of a Low-Dimensional Physical Reaction Coordinate for Calcium Binding in Troponin C

Emergence of a Low-Dimensional Energetic Landscape Governing Calcium Binding in Troponin C | 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 Emergence of a Low-Dimensional Energetic Landscape Governing Calcium Binding in Troponin C Abdul Basit This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8811918/v3 This work is licensed under a CC BY 4.0 License Status: Posted Version 3 posted You are reading this latest preprint version Show more versions Abstract Ca 2+ binding regulates muscle contraction through coordinated structural and dynamical mechanisms, yet a unified description of mutation-induced perturbations in Ca 2+ binding energetics is lacking. Mutational effects on protein are often described as high-dimensional and difficult to interpret mechanistically. We develop a physically interpretable low coordinate quantifying the coordination environment, properties of the electric field, and dynamical communications. Structural, electrostatic, and dynamical domains independently achieve Pearson correlations of R p =0.83, 0.83, and 0.85, respectively, with experimental binding free energies. Integration of these domains reproduces experimental trends with strong accuracy R p =0.90. The descriptor space suggests substantial dimensional compression consistent with a reduced representation. The model provides a framework for understanding changes in Ca 2+ binding regulatory proteins. Biophysics Troponin C Calcium signalling Elastic network models Dimensional reduction Physics-informed machine learning Full Text Additional Declarations The authors declare no competing interests. Supplementary Files rq.pdf Cite Share Download PDF Status: Posted Version 3 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. 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