Figure 2

Atomistic molecular-dynamic simulations of mutated tubulins predict their structural effects. (A) Heat maps represent Root Mean Square Deviation (RMSD) of wild-type tubulin α chain and 8 mutants (rare alleles) that reveal differences in structural stability over time. Higher RMSD values (red and orange) indicate greater structural changes, while blue and green represent the least change. B) Heat maps represent Root Mean Square Fluctuation (RMSF) across TUBA4A at residues 1–432, averaged over the course of 500-ns simulations. Numbered triangles indicate GTP-contact residues referenced in the text. All values (indicated in the key at panel right) are normalized to wild-type α tubulin (not shown; represented by deep blue-green, 0.98). (C) Molecular-structure diagrams at the final (500-ns) frame of α-tubulin mutant simulations (red) are superimposed on the wild-type structure (green), to depict structural perturbations due to mutations. The most notable structural changes are highlighted within shaded dashed ovals in mutants A383T, R215C, R320C and W407X. (D) Enlarged structural diagrams of GTP-binding regions for 6 TUBA4A mutations (with GTP-interacting residues highlighted in yellow).