Overall structure of a survivin dimer with deeply buried dimerization core residues shown by their molecular surface in gray and noncore residues shown by sticks in green. Qi and colleagues show that the deeply buried dimerization core residues in undruggable oncogenic dimeric proteins can be targeted using computational approaches for drug discovery to destroy these proteins. Specifically, a lead small-molecule inhibitor LQZ-7F targeting the dimerization core residues of survivin was discovered that induced proteasome-dependent survivin degradation, mitotic arrest, apoptosis, and blocked the growth of human xenograft tumors. For details, see article by Qi and colleagues on page 453.