Self-assembly of polypeptides into left-handedly twisted fibril-like structures

In this paper, we investigated the spontaneous formation of aggregation structures of amyloid-forming peptide (GGVVIA) using a coarse-grained model and Monte Carlo simulations. The effects of concentration and temperature on the formation of different aggregation structures were studied. Three types of aggregation structures, single-layer β sheet, amorphous β-sheet aggregate, and fibril-like structures, were observed in our simulations. The fibril-like structures obtained in simulations have a common cross-β spine structure in which β sheets twist in a left-handed fashion. The averaged twisting angle of the β sheet in the fibril-like structures is 12°±2°. Moreover, it was found that the peptides in the same β sheets prefer to arrange in a parallel way, which is consistent with the corresponding GGVVIA crystalline structure. On the other hand, it was found that there is a rich family of β-sheet stacking patterns in the fibril-like structures suggesting that the fibril structures are more complex than the corresponding crystalline structure and there exist many local free-energy minima rather than a distinct global minimum.