Molecular dynamics simulation of the nanofibrils formed by amyloid-based peptide amphiphiles

Atomistic molecular dynamics simulations have been performed on the peptide amphiphiles (PAs) with four amyloid beta peptide fragments as head groups. The stable structures were monitored by the root mean square deviation with respect to the energy minimised initial structures. Random coil and beta-sheet structures with hydrogen bonds along and perpendicular to the long axis of the nanofibre were obtained due to the different nature of the head groups. Influences of pH and capping ends on the nanofibre structures were investigated through variation of the protonation states of the ionic amino acids in the peptides. The peptides with opposite charges on both sides were found to have the fewest beta-sheet structures, and the charges on the outer terminal tended to destruct the beta-sheets while those at the inner side did not. The isolated charge in the centre of peptides was found to be able to promote the formation of regular beta-sheets, while multiple charged residues could not support ordered beta-sheet structures. When charge neutralisation occurred between adjacent residues, regular beta-sheet laminates might also occur for systems with charges at the outer terminal. With the increase of beta-sheet structures formed, the original twisted structures found for random coil structures of the PAs could be diminished by the hydrogen bonds.