Molecular modelling to investigate relationships between protein conformation and aggregation tendency in neurodegenerative diseases.

Alzheimer’s disease (AD) is the most common presenile neurodegenerative disease. Causes of AD are not clearly elucidated yet. According to the amyloid hypothesis, amyloid beta deposits are the fundamental cause of the disease. Mutations in the Aß peptide alter the toxicity, oligomerization pathways and rate of fibril formation and can be grouped in pathogenic mutations and synthetic mutations. However, the precise mechanism of toxicity of amyloid aggregates remains unclear. Computational Molecular Modelling may help to clarify mechanisms behind aggregation and oligomerization of Aß. The present study focuses on conformational stability and mechanical properties of wild-type (WT) and mutants of amyloid β11-42. Overall, computational results here presented highlight an enhanced stability for the WT when compared to mutant types of amyloid β11-42, suggesting that specific aminoacid substitution may affect Aβ42 aggregation propensity.