Solvent Relaxation NMR: A Tool for Real-Time Monitoring Water Dynamics in Protein Aggregation Landscape

Abstract

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.

Interactions of Co, Cu, and non-metal phthalocyanines with external structures of SARS-CoV-2 using docking and molecular dynamics

“…The extent to which amino acids interact with the solvent and the protein core is proportional to the surface area exposed to the solvent. Two solvation models can perform MD simulations of solvated systems: the explicit solvation model and the implicit solvation model 95 . Empirical methods, such as the SASA 96 , 97 , often provide simple and fast ways to assess solvation energy with an accuracy comparable to theoretical models.…”

Protein Design: From the Aspect of Water Solubility and Stability

“…The dynamic and energetic properties of water-mediated protein interactions were characterized by comparing different interfacial interactions at residue and solvent levels, whereas the mobility, free energy, and conservation of interactions were investigated, proving the necessity of integrating solvent parameters in the development of energetic functions to describe protein–protein interactions. Bhunia and co-workers developed a tool of solvent relaxation NMR for the real-time monitoring of water dynamics in the protein aggregation landscape, and all-atom classical MD simulation was used to validate this method . MD simulation was applied to reveal a partially resembling pattern of water dynamics for fragment AV20 (A21-V40) of amyloid system Aβ40.…”

“…Bhunia and co-workers developed a tool of solvent relaxation NMR for the real-time monitoring of water dynamics in the protein aggregation landscape, and all-atom classical MD simulation was used to validate this method. 797 MD simulation was applied to reveal a partially resembling pattern of water dynamics for fragment AV20 (A21-V40) of amyloid system Aβ40.…”

Folding Mechanism and Aggregation Propensity of the KH0 Domain of FMRP and Its R138Q Pathological Variant

“…Different studies emphasized the relevance of partially folded states in the aggregation process and in amyloid fibril formation [ 32 , 33 , 34 , 35 ]. In the case of the KH0 domain from FMRP, we were initially prompted to explore the propensity of KH0 and KH0-R138Q to form fibrillar-like aggregates in vitro by the results of (i) the far-UV CD spectroscopy experiments, which clearly showed an irreversible conformational transition from the N state to β-rich species as a function of temperature and (ii) the observation that the KH0 domain, both the wt and the R138Q variant, fold through a three-state mechanism, implying the formation of a transient intermediate.…”