Figure 1. . Structure-based design strategy.

(A) Molecular surface representation of the p53 mutant Y220C in complex with the carbazole-based molecule PK083 (Protein Data Bank ID: 2VUK), highlighting different subsites of the binding pocket. Subsite 2 is not occupied by the ligand. The side chain of Cys220 blocks access to subsite 3 in the complex with PK083. Two different orientations are shown: cross-section through the binding site (top) and top view (bottom). (B) Scheme showing the design strategy for improving the binding affinity of PK083 by targeting subsite 2. See text for further details.