  Toxic fibrillar aggregates of Islet Amyloid PolyPeptide (IAPP) appear as the
physical outcome of a peptidic phase-transition signaling the onset of type-2
diabetes mellitus in different mammalian species. In particular, experimentally
verified mutations on the amyloidogenic segment 20-29 in humans, cats and rats
are highly correlated with the molecular aggregation propensities. Through a
microcanonical analysis of the aggregation of IAPP_{20-29} isoforms, we show
that a minimalist one-bead hydrophobic-polar continuum model for protein
interactions properly quantifies those propensities from free-energy barriers.
Our results highlight the central role of sequence-dependent hydrophobic
mutations on hot spots for stabilization, and so for the engineering, of such
biological peptides.
