The degree of predicted structural disruption correlates well with the clinical severity induced by the mutation.

For each of the 17 mutations in the self-association domain that were modeled (Table 1), the RMSΔ of their backbone structure versus that of the Drosophila crystal structure was plotted versus an estimate of the clinical severity of the condition, on a scale of 0 to 4 (as described in “Materials and methods”). Also included in this plot is the RMSΔ value for the native structure (2.846 Å, clinical severity = 0). Note that the deviation of the mutant structures, as predicted by dynamic molecular modeling from a knowledge of the primary sequence and the crystal structure of Drosophila spectrin, correlates well with the clinical severity of each mutation. This behavior can be approximated by the equation shown, derived by a nonlinear least squares fit to the data.