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

This study investigated the impact of point mutations on the structural stability of coiled coil fragments in human hair keratin, specifically related to the hereditary hair dystrophy Monilethrix. Using molecular dynamics simulations and free energy calculations, the research focused on two mutations, Glu413Lys and Glu413Asp, in the helix termination motif of the hHb6 gene. The Glu413Lys mutation caused significant conformational changes and a large change in free energy, suggesting it could affect intermediate filament (IF) assembly or stability. In contrast, the Glu413Asp mutation resulted in a negligible free energy difference, indicating it did not impact coiled coil stability.