Conformational stability of the tetrameric de novo designed hexcoil-Ala helical bundle

We have performed molecular dynamics method to investigate the conformational stability of the homotetramer form of HexCoil-Ala (PDB Code 3S0R). The previous experiments showed that the chains tend to form tetramer structures. The system was simulated in explicit water model at several temperatures by using isobaric-isothermal ensemble to better understand the behaviour of each monomer and its tetramer form. It was observed that central residues of each monomer have highly helical percentages in comparison with the termini residues. As the temperature increased, these percentages decreased, and bend-like configurations came into being due to the fact that the C-and N-terminals of the monomer were getting closer. When free energy landscapes of HexCoil-Ala were calculated by using the distance between Leu-Zipper and Ala-Coil interface, it was seen that the assemblies of monomers were very strong. What's more, the average values obtained from them were very close to the native case between 300 K and 350 K. It was also observed that the direct salt bridge forming between the residues E8 with R25 in the other chains plays a significant role for keeping tetramer structure. Consequently, our results are in better agreement with the results of experimental observations.