Stability of the Aß42 Peptide in Mixed Solutions of Denaturants and Proline.

Amyloid ß-peptide (Aß) is responsible for the neuronal damage and death of a patient with Alzheimer's disease (AD). Aß42 oligomeric forms are dominant neurotoxins and are related to neurodegeneration. Their different forms are related to various pathological conditions in the brain. We investigated Aß42 peptides in different environments of proline, urea, and GdmCl solutions (in pure and mixed binary forms) through atomistic molecular dynamics simulations. Preferential exclusion from the protein surface and facile formation of a large number of weak molecular interactions are the driving forces for the osmolyte's action. We have focused on these interactions between peptide monomers and pure/mixed osmolytes and denaturants. Urea, as usual, denatures the peptide strongly compared to the GdmCl by accumulation around the peptide. GdmCl shows lesser build-up around protein in contrast to urea but is involved in destabilizing the salt bridge formation of Asp23 and Lys28. Proline as an osmolyte protects the peptide from aggregation when mixed with urea and GdmCl solutions. In mixed solutions of two denaturants and osmolyte plus denaturant, the peptide shows enhanced stability as compared to pure denaturant urea solution. The enhanced stability of peptides in proline may be attributed to its exclusion from the peptide surface and favoring salt bridge formation.