Dynamical Manifestations of Supercooling in Amyloid Hydration

Abstract

The effect of extreme temperature on amyloidogenic species remains sparsely explored. In a recent study (J. Phys. Chem. Lett., 2019, 10, (10)), we employed exhaustive molecular dynamics simulations to explore the cold thermal response of a putative small amyloid oligomer and to elicit the role of solvent modulation. Herein, we investigate the dynamical response of the hydration waters of the oligomer within the supercooled states. Using NMR-based formalism, we delineate the entropic response in terms of the side-chain conformational entropy that corroborates the weakening of the hydrophobic core with lowering of temperature. The translational dynamics of the protein and hydration waters reveal the coupling of protein dynamical fluctuations with solvent dynamics under supercooled conditions. Probing the translational motion as a space–time correlation indicates glassy dynamics exhibited by hydration waters in the supercooled regime. Caging of the water molecules with lowering of temperature and the resultant hopping dynamics are reflected in the longer β-relaxation timescales of translational motion. Furthermore, we utilized mode-coupling theory (MCT) and derived the ideal glass transition temperature from translational and rotational dynamics, around ∼196 and 209 K, respectively. Interestingly, rotational motion in the supercooled regime deviates from the MCT law, exhibits Arrhenius motion, and marks a fragile-to-strong crossover at 227 K. The low-frequency vibrational modes also coincide with the dynamical transition. This exposition lends dynamical insights into the hydration coupling of an amyloid aggregate under cryogenic conditions.

Effects of External Perturbations on Protein Systems: A Microscopic View

“…Furthermore, the cold thermal response to amyloid assemblies was studied using exhaustive simulations, unlike protein monomers, which show almost a linear increase in oligomeric stability with decreasing temperature below ∼250 K (Figure B) . Signatures of the transitions were also observed in the dynamical behavior of the hydration layer …”

“… 87 Signatures of the transitions were also observed in the dynamical behavior of the hydration layer. 88 …”

“…87 Signatures of the transitions were also observed in the dynamical behavior of the hydration layer. 88 Molecular simulations have revealed that the high-temperature stability in thermophilic proteins are attained with a combination of high secondary structure propensity, with a higher number of salt bridges, disulfide bonds, and intramolecular hydrogen bonds contributing in a more compact hydrophobic core formation in comparison to the mesophilic proteins. 90−93 in cold temperatures share an overall unstable fragile structure that is stabilized with a small number of weak intramolecular interactions.…”

Influence of ice formation on the dynamic and thermodynamic properties of aqueous solutions

“…The study of water mixtures with diverse solutes (polymers [1,2], biopolymers [3][4][5][6], salts, amino acids [4,7] or other liquids [8]) is essential in technological applications and crucial to different phenomena connected with life (those involving proteins and other biomolecules in crowded solutions). Therefore, this field remains under intense investigation.…”