Template induced conformational change of amyloid-β monomer.

Population of aggregation-prone conformers for the monomeric amyloid-β (Aβ) can dramatically speed up its fibrillar aggregation. In this work, we study the effect of preformed template on the conformational distributions of the monomeric Aβ by replica exchange molecular dynamics. Our results show that the template consisting of Aβ peptides with cross-β structure can induce the formation of β-rich conformations for the monomeric Aβ, which is the key feature of the aggregation-prone conformers. Similar effect is observed when the hIAPP peptides and poly alanine peptides were used as templates, suggesting that the template effect is insensitive to the sequence details of the template peptides. In comparison, the template with helical structure has no significant effects on the β-propensity of the monomeric Aβ. Analysis to the interaction details revealed that the template tends to disrupt the intrapeptide interactions of the monomeric Aβ, which are absent in the fibrillar state, suggesting that the preformed template can reorganize the intrapeptide interactions of the monomeric Aβ during the capturing stage and reduce the energy frustrations for the fibrillar aggregations.