Structural Stability of Wild Type and Mutated Alpha-Keratin Fragments: Molecular Dynamics and Free Energy Calculations

The study examined the effects of point mutations on the structural stability of coiled coil fragments in human hair intermediate filaments, specifically focusing on the helix termination motif of the keratin gene hHb6 linked to Monilethrix, a hereditary hair dystrophy. Using molecular dynamics simulations and free energy calculations, it was found that the Glu413Lys mutation led to significant conformational changes and a substantial change in free energy, suggesting a potential impact on filament assembly or stability. Conversely, the Glu413Asp mutation showed a negligible free energy difference, indicating no effect on coiled coil stability.