Investigation of alpha-keratin intermediate filament structure by molecular dynamic simulation

Molecular dynamic simulations are carried out in order to investigate the stability of the secondary and tertiary structure of the intermediate filaments monomer unit of wool. Based on the assumed secondary structure three segments of the primary structure are selected: 1A, L1,2 and a part of 2B. With the ideal alpha-helix as start conformation, the simulations are carried out with the MD-algorithm of DISCOVER 2.9.0 (BIOSYM, 1993) and the CFF91 force field for 500 ps at different temperatures in vacuum. In either simulation a destabilization of the helical structure with an increase of the simulation temperature is observed. By monitoring the length distribution of the axially oriented (O...H)-hydrogen bonds, which stabilize the helical structure, transition temperatures for the alpha-helical denaturation are determined. The supposedly alpha-helical segments 1A and 2B show significantly higher transition temperatures than segment L1,2. This lower temperature confirms the expectation from the amino acid sequence that the linker segment shows more conformational flexibility and is nonhelical at room temperature.