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 beta sheet, amorphous beta-sheet aggregate, and fibril-like structures, were observed in our simulations. The fibril-like structures obtained in simulations have a common cross-beta spine structure in which beta sheets twist in a left-handed fashion. The averaged twisting angle of the beta sheet in the fibril-like structures is 12 degrees +/-2 degrees. Moreover, it was found that the peptides in the same beta 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 beta-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.
Mu
Yan
Y
Department of Chemistry, Texas A&M University, College Station, Texas 77843, USA.
Gao
Yi Qin
YQ
D000595:Amino Acid Sequence; D008958:Models, Molecular; D009010:Monte Carlo Method; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D013696:Temperature
D010455:Peptides