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

Antibody–drug conjugate programs often select epitopes before peptide-level mapping is available. Here I describe a reproducible molecular dynamics (MD) workflow for pre-HDX epitope triage in EGFR and HER2, evaluated on three therapeutic antibody–antigen pairs (EGFR–cetuximab, HER2–trastuzumab, EGFR–panitumumab). For each system, matched apo (antigen-only) and holo (Fab-bound) trajectories are reduced to residue-consistent antigen-only inputs and summarized into sliding peptide windows (W=12, stride=4) to generate a ranked list intended to guide first-pass HDX-MS peptide panel design.