Aqueous urea solution destabilizes Abeta(16-22) oligomers.

Area of Science:

• Biochemistry
• Molecular Biophysics
• Computational Chemistry

Background:

• Amyloidogenic peptides, such as Abeta(16-22), are prone to forming oligomeric structures implicated in diseases.
• The role of denaturants like urea in modulating peptide aggregation and stability is crucial for understanding disease mechanisms and developing therapeutic strategies.

Purpose of the Study:

• To investigate the effect of aqueous urea solutions on the stability of Abeta(16-22) peptide oligomers.
• To elucidate the molecular mechanisms underlying urea-induced destabilization of these peptide structures.

Main Methods:

• Utilized long multiple trajectories from molecular dynamics simulations.
• Employed two different urea models to ensure robustness of findings.
• Analyzed peptide backbone interactions and secondary structure formation.

Main Results:

• High urea concentrations promote beta-strand formation in Abeta(16-22) monomers, contrasting with compact random coil structures in water.
• Urea destabilizes stable antiparallel beta-sheet structures of tripeptide systems.
• Direct urea-peptide backbone interactions enhance beta-strand content and disrupt oligomeric structures.

Conclusions:

• Oligomer unbinding dynamics are influenced by opposing effects: increased monomer beta-strand propensity and rapid oligomer disruption.
• The destabilization mechanism relies on hydrogen bond formation between urea and the peptide backbone.
• High urea concentrations are predicted to destabilize oligomers of other amyloidogenic peptides.