Mathematical Quantification of Binding Complementarity using Intersection Surface Area (ISA) and Geometric Sensitivity Index (GSI)

Mathematical Quantification of Binding Complementarity using Intersection Surface Area (ISA) and Geometric Sensitivity Index (GSI) | 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 Mathematical Quantification of Binding Complementarity using Intersection Surface Area (ISA) and Geometric Sensitivity Index (GSI) GRACE KIM, DONGYUNG KIM This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9509472/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract The R292K mutation in Influenza Neuraminidase (NA) significantly hinders the efficacy of clinical inhibitors, yet the physical basis of this resistance remains under-explored. In this study, we introduce a novel computational framework integrating Molecular Dynamics (MD) simulations with a geometric Intersection Surface Area (ISA) model. Our results demonstrate that the R292K mutation induces a structural destabilization characterized by a ∼11.5 kcal/mol increase in binding free energy and a 15 − 21% reduction in intersection binding volume (V bind). Notably, Zanamivir (Ligand D) exhibited the highest geometric sensitivity with a 27.2% reduction in V bind , providing a definitive structural explanation for its clinical resistance. This integrated geometric-MD approach offers a robust, high-throughput predictive tool for optimizing next-generation neuraminidase inhibitors against evolving viral mutants. Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 17 May, 2026 Reviews received at journal 11 May, 2026 Reviews received at journal 09 May, 2026 Reviewers agreed at journal 08 May, 2026 Reviewers agreed at journal 07 May, 2026 Reviewers agreed at journal 05 May, 2026 Reviewers agreed at journal 04 May, 2026 Reviewers invited by journal 04 May, 2026 Editor assigned by journal 04 May, 2026 Submission checks completed at journal 28 Apr, 2026 First submitted to journal 23 Apr, 2026 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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