Figure 5. Comparison of calculated ΔΔG^mut values for mutant ZMPSTE24 alleles with experimental data for ZMPSTE24 stability and prelamin A cleavage activity from Fig. 4B and Fig.4C.

ΔΔG^mut is the predicted difference in free energy of folding between a WT and mutant protein. A) The calculated ΔΔG^mut values in Rosetta Energy Units (REU) (y axis) for the indicated mutant alleles of ZMPSTE24 is compared with the level of ZMPSTE24 stability (denoted as expression; × axis) from the assay shown in Fig 4B. When the proline mutation L94P is excluded, the correlation coefficient is −0.843. (B) Comparison of ΔΔG^mut calculations (y axis) with percentage of prelamin A cleavage determined in Fig. 4A (x axis). When the proline mutation L94P is excluded, the correlation coefficient is −0.207. Disease variants are in red and additional variants are in blue. Horizontal error bars are the standard deviation of the mean taken from Fig 4.