Exploring the Counteracting Mechanism of Trehalose on Urea Conferred Protein Denaturation: A Molecular Dynamics Simulation Study

Abstract

To provide the underlying mechanism of the inhibiting effect of trehalose on the urea denatured protein, we perform classical molecular dynamics simulations of N-methylacetamide (NMA) in aqueous urea and/or trehalose solution. The site-site radial distribution functions and hydrogen bond properties indicate in binary urea solution the replacement of NMA-water hydrogen bonds by NMA-urea hydrogen bonds. On the other hand, in ternary urea and trehalose solution, trehalose does not replace the NMA-urea hydrogen bonds significantly; rather, it forms hydrogen bonds with the NMA molecule. The calculation of a preferential interaction parameter shows that, at the NMA surface, trehalose molecules are preferred and the preference for urea decreases slightly in ternary solution with respect to the binary solution. The exclusion of urea molecules in the ternary urea-NMA-trehalose system causes alleviation in van der Waals interaction energy between urea and NMA molecules. Our findings also reveal the following: (a) trehalose and urea induced second shell collapse of water structure, (b) a reduction in the mean trehalose cluster size in ternary solution, and (c) slowing down of translational motion of solution species in the presence of osmolytes. Implications of these results for the molecular explanations of the counteracting mechanism of trehalose on urea induced protein denaturation are discussed.

Pressure–Volume–Temperature Relationships for Aqueous Solutions of N-Methylacetamide at Temperatures Ranging from 278.15 to 323.15 K and Pressures up to 100 MPa

“…Studies on N -methylacetamide (NMA) play an important role in chemistry and biochemistry since it is one of the simplest amides that is used as a model for the study of peptide bonds. − Aqueous solutions of N -methylacetamide were previously used as model systems that emitted the interaction of a peptide backbone and water, − and therefore, these solutions are the center of attention and have been actively studied by various theoretical and experimental methods. − …”

Understanding The Role of Reline, a Natural DES, on Temperature-Induced Conformational Changes of C-Kit G-Quadruplex DNA: A Molecular Dynamics Study

“…Considering previous studies, , the first solvation shell (FSS) of biomolecules can be described as the number of the solvent molecules present at a distance of 3.5 Å from the biomolecule surface. In more detail, if any heavy atoms of a solvent are present within 3.5 Å of any heavy atom of a residue of G-quadruplex DNA, it will be considered as a molecule which is present in a first solvation shell.…”

Effect of Osmolytes on Conformational Behavior of Intrinsically Disordered Protein α-Synuclein

“…9 B). It has also been known from the previous studies that the protecting/stabilizing osmolytes have less direct interaction with the proteins and increases the structural stability of the protein by accumulating in the hydrophobic regions of the proteins (39,68,69). The interaction between protein backbone and TMAO is highly unfavorable (70).…”