Computational analysis of the effect of [Tea][Ms] and [Tea][H2PO4] ionic liquids on the structure and stability of Aβ(17-42) amyloid fibrils

Experimental studies have reported the possibility of affecting the growth/dissolution of amyloid fibres by the addition of organic salts of the room-temperature ionic-liquid family, raising the tantalizing prospect of controlling these processes under physiological conditions. The effect of [Tea][Ms] and [Tea][H2PO4] at various concentrations on the structure and stability of a simple model of A beta 42 fibrils has been investigated by computational means. Free energy computations show that both [Tea][Ms] and [Tea][H2PO4] decrease the stability of fibrils with respect to isolated peptides in solution, and the effect is significantly stronger for [Tea][Ms]. The secondary structure of fibrils is not much affected, but single peptides in solution show a marked decrease in their beta-strand character and an increase in alpha-propensity, again especially for [Tea][Ms]. These observations, consistent with the experimental picture, can be traced to two primary effects, i.e., the difference in the ionicity of the [Tea][Ms] and [Tea][H2PO4] water solutions and the remarkable affinity of peptides for [Ms](-) anions, due to the multiplicity of H-bonds.

Automated summary

Experimental studies have shown that the addition of organic salts can affect the growth/dissolution of amyloid fibers, with a stronger effect observed for [Tea][Ms]. Computational analysis revealed that both [Tea][Ms] and [Tea][H2PO4] decrease the stability of fibrils compared to isolated peptides in solution. The secondary structure of fibrils remains largely unaffected, but single peptides in solution show changes in beta-strand character and alpha-propensity, particularly with [Tea][Ms].