Illustration of coupled folding and binding. In this illustration, an intrinsically disordered—partially helical—PUMA sequence is shown to bind to Mcl-1 and form a continuous helix in the context of the bound complex. PUMA is shown as a ribbon diagram to emphasize its helicity in the bound complex. The residues are colored as follows: Hydrophobic residues are in gray, polar residues are in green, negatively charged residues are in red, and positively charged residues are in blue. Mcl-1 is shown in a surface representation to emphasize the electrostatic potential. Regions of high positive potential are in blue, regions of high negative potential are in red, and regions with near zero electrostatic potential are in white. The electrostatic surface was computed using the Adaptive Poisson Boltzmann solver (Baker et al., 2001).