Identification of key stabilizing interactions of amyloid-β oligomers based on fragment molecular orbital calculations on macrocyclic β-hairpin peptides

Analyzing the electronic states and inter-/intra-molecular interactions of amyloid oligomers expand our understanding of the molecular basis of Alzheimer's disease arid other amyloid diseases. In the current study, several high-resolution crystal structures of oligomeric assemblies of A beta-derived peptides have been studied by the ab initio fragment molecular orbital (FMO) method. The FMO method provides comprehensive details of the molecular interactions between the residues of the amyloid oligomers at the quantum mechanical level. Based on the calculations, two sequential aromatic residues (F19 and F20) and negatively charged E22 on the central region of A beta have been identified as key residues in oligomer stabilization and potential interesting pharmacophores for preventing oligomer formation.

Automated summary

Analyzing the electronic states and inter-/intra-molecular interactions of amyloid oligomers can provide insights into the molecular basis of Alzheimer's disease. The ab initio fragment molecular orbital (FMO) method reveals key aromatic residues and negatively charged residues in Aβ oligomers, offering potential pharmacophores for preventing oligomer formation.