| Autor: |
Lee PY; Chemical Physics Program, University of Maryland, College Park, Maryland 20742, United States., Gotla S; Fischell Department of Bioengineering, University of Maryland, College Park, Maryland 20742, United States., Matysiak S; Chemical Physics Program, University of Maryland, College Park, Maryland 20742, United States.; Fischell Department of Bioengineering, University of Maryland, College Park, Maryland 20742, United States. |
| Abstrakt: |
We developed a coarse-grained model for the protic ionic liquid, triethylammonium mesylate ([TEA] + [Ms] - ), to characterize its inhibitory effects on amyloid aggregation using the K 16 LVFFAE 22 fragment of the amyloid-β (Aβ 16-22 ) as a model amyloidogenic peptide. In agreement with previous experiments, coarse-grained molecular dynamics simulations showed that increasing concentrations of [TEA] + [Ms] - in aqueous media led to increasingly small Aβ 16-22 aggregates with low beta-sheet contents. The cause of [TEA] + [Ms] - 's inhibition of peptide aggregation was found to be a result of two interrelated effects. At a local scale, the enrichment of interactions between [TEA] + cations and hydrophobic phenylalanine side chains weakened the hydrophobic cores of amyloid aggregates, resulting in poorly ordered structures. At a global level, peptides tended to localize at the interfaces of IL-rich nanostructures with water. At high IL concentrations, when the IL-water interface was large or fragmented, Aβ 16-22 peptides were dispersed in the simulation cell, sometimes sequestered at unaggregated monomeric states. Together, these phenomena underlie [TEA] + [Ms] - 's inhibition of amyloid aggregation. This work addresses the critical lack of knowledge on the mechanisms of protein-ionic liquid interactions and may have broader implications for industrial applications. |
