Engine: Boltz-2 (structure prediction) + SolubleMPNN (sequence design), 5 cycles per full trajectory. Tournament per epitope combo: R1 — 100 seeds × 1 cycle, keep top 40% by ipTM (40 survive). R2 — 40 seeds × 2 cycles, keep top 20 based on trajectory improvement and high ipTM baseline. R3 — 20 seeds × 2 cycles, full 5-cycle refinement. 220 cycle-equivalents per combo × 4 epitope combos = 880 total designs. Epitope combos: C1 (GLMN-competitive), C2 (CRL state-selective), C3 (Extended E2 face), C4 (Full E2 sweep). Hotspot contacts: polar-only, all 12 Zn-coordinating residues excluded. No Cys in binder. Size range: 70–150 AA. Hardware: single A100 GPU.