Breakout character of islet amyloid polypeptide hydrophobic mutations at the onset of type-2 diabetes
arXiv:1411.1672 · doi:10.1103/PhysRevE.90.052716
Abstract
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.
arXiv comment8 pages, 6 figures, 1 table; final version to appear in Physical Review E
References in corpus (11)
- Multicanonical Ensemble: A New Approach to Simulate First-order Phase Transitions
- Microcanonical Analyses of Peptide Aggregation Processes
- Multicanonical Simulations Step by Step
- Topological Solitons and Folded Proteins
- A Gauge Field Theory of Chirally Folded Homopolymers with Applications to Folded Proteins
- Microcanonical versus Canonical Analysis of Protein Folding
- The spectrum of screening masses near T_c: predictions from universality
- Microcanonical thermostatistics of coarse-grained proteins with amyloidogenic propensity
- Screening masses in the SU(3) pure gauge theory and universality
- Screening masses in the SU(3) pure gauge theory and universality
- Screening masses in quenched (2+1)d Yang-Mills theory: universality from dynamics?
Cited by in corpus (4)
- Microcanonical characterization of first-order phase transitions in a generalized model for aggregation
- PHAST: Protein-like heteropolymer analysis by statistical thermodynamics
- Shape-free theory for the self-assembly kinetics in macromolecular systems
- Evolution and Pathogenicity of SARS-CoVs: A Microcanonical Analysis of Receptor-Binding Motifs