De novo binder design targeting RBX1 using hotspot-conditioned RFdiffusion backbone generation from the RBX1-containing complex (PDB: 1LDJ), followed by ProteinMPNN sequence design. Candidates were filtered using explicit biophysical heuristics, screened for monomer foldability with ESMFold (mean pLDDT > 75), and prioritised using Boltz-2 complex predictions with pair_iptm_AB as the primary ranking metric. Monomer and complex confidence metrics were used for prioritisation only and not interpreted as direct measures of binding affinity.