Expansion of polyglutamine (polyQ) sequence in some proteins leads to their aggregation, which is responsible
for neurodegenerative diseases like Huntington’s disease, ataxia etc. A flanking domain is usually fused at the N-terminal
to polyQ in these proteins. On linking the flanking residues to polyQ, they accelerate aggregation of the proteins, which
initiates from the flanking residues. In this report the inherent propensity of the flanking residues towards aggregation in
six aggregating proteins has been elucidated from their primary sequences with the help of Betascan and PASTA programs
and explored unambiguously. This will provide a molecular mechanism of this process. Suppression of aggregation using
chaperones like αB-crystallin by masking the exposed hydrophobic surface of flanking residues is also documented
through molecular docking, which could be applied for inhibition of aggregation of this type of proteins.