Cold Thermal Response of an Amyloid Oligomer Differs from Typical Globular Protein Cold Denaturation.

In contrast with the general behavior of folded proteins, cold thermal response of amyloid assemblies is difficult to elicit with simple models. We exploit exhaustive simulations to evaluate the thermal response of a barrel-shaped model amyloid oligomer, with a distinct hydrophobic core akin to that of folded proteins. Cumulative thermal data over 210 to 483 K indicate a sharp inflexion and rise in structural stability as the temperature is lowered below the melting temperature of the water model. This is not commensurate with the equilibrium free energy profile obtained with core packing as the order parameter. However, energetic analyses and size of their fluctuations indicate crucial role of hydration in mediating structural transitions, beyond the expected temperature-dependent hydrophobic effect. Structural ordering of the hydration layer over bulk water maximizes at the transition and vanishes at high temperatures. This is a first direct demonstration of the microscopic influence of hydration water on the low temperature response of an amyloid assembly close to the cryo-regime.