  Deciphering the links between amino acid sequence and amyloid fibril
formation is key for understanding protein misfolding diseases. Here we use
Monte Carlo simulations to study aggregation of short peptides in a
coarse-grained model with hydrophobic-polar (HP) amino acid sequences and
correlated side chain orientations for hydrophobic contacts. A significant
heterogeneity is observed in the aggregate structures and in the thermodynamics
of aggregation for systems of different HP sequences and different number of
peptides. Fibril-like ordered aggregates are found for several sequences that
contain the common HPH pattern while other sequences may form helix bundles or
disordered aggregates. A wide variation of the aggregation transition
temperatures among sequences, even among those of the same hydrophobic
fraction, indicates that not all sequences undergo aggregation at a presumable
physiological temperature. The transition is found to be the most cooperative
for sequences forming fibril-like structures. For a fibril-prone sequence, it
is shown that fibril formation follows the nucleation and growth mechanism.
Interestingly, a binary mixture of peptides of an aggregation-prone and a
non-aggregation-prone sequence shows association and conversion of the latter
to the fibrillar structure. Our study highlights the role of sequence in
selecting fibril-like aggregates and also the impact of structural template on
fibril formation by peptides of unrelated sequences.
