Molecular dynamics approach to understand the denaturing effect of a millimolar concentration of dodine on a λ-repressor and counteraction by trehalose

Abstract

Commonly used denaturants for protein denaturation are conventionally required in high concentrations in order to produce their effects. In this study, a molecular dynamics simulation of a mutated version of the N-terminal domain of a λ-repressor is carried out in the presence of a 10 millimolar (mM) concentration of dodine. Such a small concentration is found to be effective for denaturation of the protein. Both electrostatic and van der Waals interactions (between protein and dodine) play a role in the denaturation process and we observe more denaturation at the terminal helices. Three different molar concentrations of trehalose are used in order to check the counteraction against the action of dodine. This study shows that 0.5 and 1.0 M trehalose are sufficient to counteract the action of dodine. The study also sheds light on the fact that some protein sites are more responsive to unfolding, which is evident from the helical fractions of the terminal helices for different systems. The counteraction of trehalose on dodine-induced protein denaturation is found to be due to the replacement of some of the dodine molecules by trehalose molecules in the solvation shell of the protein. Preferential solvation of dodine molecules by trehalose molecules through hydrogen bonding interactions also plays a vital role in stabilizing the native conformation of the protein in a high trehalose concentration. Replacement of protein-dodine and protein-water hydrogen bonds by protein-trehalose hydrogen bonds is also observed.

Potential of a Natural Deep Eutectic Solvent, Glyceline, in the Thermal Stability of the Trp-Cage Mini-protein

“…Hence we have plotted the evolution of the average number of hydrogen bonds within the Trp-cage mini-protein with time (see Figure S11 (of the Supporting Information)). A hydrogen bond is considered when the distance between the donor (D) and acceptor (A) is within 3.5 Å and the D–A–H angle is within 45°. ,,,,− Here it can been seen that the values of hydrogen bonds for G300–G400 systems almost correspond to each other, with a negligible decreasing trend with increasing temperature. However, for G450, the hydrogen bond number decreases by a noticeable amount.…”

“…A satisfactory value of electrostatic energy refers to direct contact via hydrogen bonds or other electrostatic interactions. Similarly, a desirable value of van der Waals energy suggests that dispersion interactions will be beneficial. , …”

“…Similarly, a desirable value of van der Waals energy suggests that dispersion interactions will be beneficial. 90,91 In Table 2, we have shown the average electrostatic and vdW energies for Trp-cage mini-protein and glyceline molecules interactions for all the systems. Protein−DES interactions are strongly regulated by electrostatic energy.…”

Mechanistic Aspects of Fungicide-Induced DNA Damage: Spectroscopic and Molecular Dynamics Simulation Studies

“…A total of 22 sodium ions were used in the simulation to neutralize the system for both cases. DNA was described using AMBER99sb-ildn force field, whereas generalized AMBER force field (GAFF) was used for dodine as it is well known that GAFF is suitable for the description of small molecules as used in earlier studies. − …”

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.…”