A reproducible molecular dynamics benchmark for ADC epitope triage in EGFR and HER2

A reproducible molecular dynamics benchmark for ADC epitope triage in EGFR and HER2 | 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 A reproducible molecular dynamics benchmark for ADC epitope triage in EGFR and HER2 hoosdally shakeel This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8820222/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Antibody–drug conjugate programs often commit to an epitope before peptide–level experimental evidence is available. I present a reproducible molecular–dynamics benchmark for pre–HDX epitope triage in EGFR and HER2, evaluated on three therapeutic antibody–antigen pairs (HER2–Trastuzumab, EGFR–Cetuximab, and EGFR–Panitumumab). For each system, paired simulations of antigen alone and antibody–bound antigen are summarized into ranked antigen regions suitable for designing an initial HDX–MS peptide panel. Performance is quantified with rank–based enrichment metrics appropriate for imbalanced labels, together with uncertainty estimates where panel size is small. For systems with published peptide–level HDX–MS labels (HER2–Trastuzumab and EGFR–Cetuximab), ranked regions are compared to reported protection patterns. For EGFR–Panitumumab, where peptide–level HDX–MS labels are not used here, evaluation is performed against proxy labels derived from structural contacts and mutational mapping of the EGFR domain III footprint. This work is framed as a reproducible benchmarking and triage layer rather than a predictor of absolute deuterium uptake or clinical efficacy. Success is defined as enrichment of known or proxy–positive regions near the top of the ranked list under a locked evaluation protocol. Structural Biology antibody–drug conjugates epitope triage molecular dynamics solvent accessible surface area HDX–MS pre–screening EGFR HER Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted 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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