Figure 1. The cold and hot denatured states of frataxin are structurally different.

(a) Structure of the native state of frataxin. (b) Free energy surface of the cold denatured state (CDS) determined at 272 K as a function of the sketch-map⁶³ collective variables that describe the conformational features of the ensembles (see Methods). Nine microstates are shown representing the local and global minima. These microstates comprise >90% of the total population. (c) Free energy surface of the hot denatured state (HDS) determined at 323 K as a function of the same two collective variables. Sixteen microstates are shown representing the local and global minima. These microstates comprise >90% of the total population (see Methods). (d,e) Secondary structure populations of the CDS (d) and HDS (e). α-Helices are represented in blue, β-strands in red and polyproline II in green; free energies are given in kJ/mol.