The Effect of Ethanol on Mutant Human Prion Protein using Molecular Dynamics Simulations

Abstract

As you know that monohydric alcohols have a great effect on protein structure, and human prion diseases are caused by conformational changes from their natural form to a misfolded state. To illustrate the effect of monohydric alcohols on the structural stability of the mutation V210I, we used the molecular dynamics method to study the dynamic features of single point mutation V210I and mutation V210I with ethanol solution. Our findings show that, while the models' global three-dimensional structure remains relatively unchanged over simulation, the mutation V210I causes local structural and secondary structure alterations, as well as global flexibility modifications. On the other hand, the existence of ethanol molecules results in overall stability compared to others simulations, exhibiting favourable dynamical properties in the secondary structure, solvent accessible surface, and salt bridges, and inhibiting the misfolding of the human prion protein. In conclusion, the simulation suggests that alcohol may provide a feasible idea in the future in-depth study of the transformation mechanism of the prion protein.