Solvent dynamics strongly induce the fibrillation of an amyloidogenic system. Probing the solvation mechanism is crucial as it enables us to predict different proteins' functionalities, such as the aggregation propensity, structural flexibility, and toxicity. This work shows that a straightforward NMR method in conjunction with phenomenological models gives a global and qualitative picture of water dynamics at different concentrations and temperatures. Here, we study amyloid system Aβ40 and its fragment AV20 (A21-V40) and G37L (mutation at Gly37 → Leu of AV20), having different aggregation and toxic properties. The independent validation of this method is elucidated using all-atom classical MD simulation. These two state-of-the-art techniques are pivotal in linking the effect of solvent environment in the near hydration-shell to their aggregation nature. The time-dependent modulation in solvent dynamics probed with the NMR solvent relaxation method can be further adopted to gain insight into amyloidogenesis and link with their toxicity profiles.
Keywords: Amyloidogenesis; amyloid beta; classical simulation; hydration-dynamics; solvent relaxation; toxicity.