Target: RBX1 RING domain. Backbone generation: RFdiffusion with E2-surface hotspots only; helical campaigns only. Sequence design: LigandMPNN (zinc-aware), temperature 0.2, 16 sequences per backbone, amino acid biases A:-3.0, W:+2.0, Y:+1.5, F:+1.0, I:+0.5, V:+0.3, C:-999.0. Filtering: sequence quality filters and AF2 monomer screen (pLDDT >= 85). Final selection: AF3 validation with ipSAE_d0chn as the primary ranking metric, gate-based filtering for clash-free models, disorder <= 10%, binder pTM >= 0.70, RBX1 pTM >= 0.70, and diversity capped at 5 sequences per backbone.