Dissecting the role of glutamine in seeding peptide aggregation

Poly glutamine and glutamine-rich peptides play a central role in plethora of pathological aggregation events. However, biophysical characterization soluble oligomers -the most toxic species involved these processes- remains elusive due to their structural heterogeneity dynamical nature. Here, we exploit the high spatio-temporal resolution coarse-grained simulations as computational microscope characterize propensity morphology series polyglutamine peptides. Comparative analysis ab-initio pinpointed double for glutamines. In first phase, glutamines mediate seeding by pairing monomeric peptides, which serve primers higher-order nucleation. According content, low molecular-weight may then proceed create larger aggregates. Once within aggregates, buried continue maturation optimizing solvent-protected hydrogen bonds networks.