A secondary structure analysis of the full conformational ensembles predicted by the above free energy surfaces indicate that binding of AM-7209 to WT significantly increases helicity of residues 21-25 (Figure , first and second rows). By contrast binding of AM-7209 to I19G is associated with only a small increase in helical propensity for residues 21-25 (Figure , third and fourth rows). As reported previously, the DSSP algorithm doesn't detect the strand component of the helix-turn-strand motif in the ordered MDM2 lid IDR (Figure , second row) around residues 12-16. Nevertheless adoption of an extended conformation for lid residues 12-16 is apparent from visualisation of the free energy surfaces (Figure ) and consistent with the increased b-strand propensity for residues 12-16 inferred from secondary chemical shift changes (Figures ). The helix propensity around residues 10-17 observed in Figure is associated with transient helices seen in closed lid conformations that wrap above the ligand (e.g. Figure label C12).