A reproducible molecular dynamics benchmark for ADC epitope triage in EGFR and HER2 Hoosdally shakeel Ministry of education and higher tertiary scientific research

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.