Effects of hydrophobic force on secondary structure of the most effective peptide in Alzheimer's disease

Introduction & objective: Changing the secondary structure of Amyloid β-peptide (1-42) is one of the most important factors in developing Alzheimer's disease. In other hand, experimental and theoretical studies confirmed that hydrophobic force has major contributors to the changing the secondary structure of amyloid beta peptide. In this work, molecular dynamic simulation used to investigate hydrophobic force effects on secondary structure of N-terminal truncated amyloid beta peptide 1-42.Material & methods: The first ten residues at the N-terminal of the peptide are polar in nature. These residues are located on the outside of the nerve cell membrane and have random coil structure. Thus, they have high dynamics. Therefore, these residues were deleted to amplify the hydrophobic forces in the peptide. By manipulating the Lennard-Jones potential, the hydrophobic forces increased or decreased. Then, the effect of these changes on the peptide secondary structure was traced. Two force fields GROMOS96 and OPLS-AA were used to perform the calculations. All molecular dynamics simulations were performed by GROMACS software.Results: The root mean square deviation (RMSD) calculation showed that the simulated systems were in equilibrium. The obtained results based on the RMSD values showed that the structure is more sensitive to OPLS-AA force field changes. The results showed that the use of force field OPLS-AA creates a more disordered secondary structure.Conclusion: With the strengthening of the repulsive forces in the potential of Lenard Jones, followed by increased hydrophobic forces the Amyloid β-peptide (1-42) secondary structure disorder is further compounded.

کلیدواژه ها:

Alzheimer disease ، hydrophobic ، molecular interaction ، force field