Fig. 1.

Computational design of peptide targeting FOXO4. a, Domains of FOXO4 and TP53 (p53). FOXO4FH (PDB ID: 3L2C), in its closed state, interacts with FOXO4CR3. TP53DBD (PDB ID: 3KMD), disrupts this intramolecular interaction and binds both FOXO4FH and FOXO4CR3. The FH epitope (87-120) which was used to design the senolytic peptide ES2 is coloured red and framed with dashed lines. Protein-protein docking analysis of b, FOXO4CR3-TP53DBD, c, FOXO4FH-TP53DBD and d, FOXO4FH-CR3. The TP53DBD is colored gray, FOXO4FH is green and FOXO4CR3 is blue. The FOXO4 epitope used to design the senolytic peptide ES2 is coloured red. For b, c and d the binding free energy ($\Delta G_{bind}$) of the complexes which were predicted by MM-GBSA is given. See also Fig. S1 and S2 and Table S1 and S2.