Molecular Mechanics of Disulfide Bonded Alpha-Helical Protein Filaments

Keratin, an alpha-helical protein, is an abundant material that forms the basis of hair and hoof, and is a composite of alpha-helical coiled coils with dense disulfide bonding between helical protein domains. Here, we report a molecular analysis of the mechanics of disulfide bonded alpha-helical protein filaments, focusing on a systematic assessment of structure-property relationships and deformation and failure mechanisms, carried out using a full atomistic explicit water model based on the CHARMM force field, extended here to capture the breaking of disulfide bonds in varied chemical microenvironments. By considering a three-strand alpha-helical model of an assembly of disulfide bonds under an external loading, we demonstrate that weak disulfide cross-link results in a highly cooperative behavior. Strong disulfide bonding resist greater external load, but the cooperative behavior is reduced. We compare the mechanical behavior of the disulfide bonded systems to a molecule with weaker H-bonds between alpha-helix domains. Under mechanical loading, H-bonds between the protein filaments are easily sacrificed and the alpha-helical structure is maintained, but the system has a lower strength. Our atomistic models provide fundamental insight into the effect of disulfide cross-link on mechanical properties of alpha-helix-based protein filament and reveals that the dependence of disulfide bond strength on the chemical microenvironment enables a tunable fiber strength by a factor of approximate to 2.5.