Effect of external electrostatic field on the stability of β sheet structures

Abstract

To explore the effect of an external electrostatic field (EEF) on the stability of protein conformations, the molecular dynamic modeling approach was applied to evaluate the effect of an EEF along the x or y direction on a water cluster containing a parallel or antiparallel β sheet structure. The β sheet structure contained two strands with a (Gly)3 sequence separated by a distance d along the x direction. The mean forces between the two strands along the x direction were computed from the trajectories of molecular dynamics simulations. In the absence of the EEF, the forces between the two strands in vacuum were repulsive and attractive in the parallel and antiparallel β sheet structures, respectively. In contrast, the mean forces between the two strands in water were attractive in both the parallel and antiparallel β sheet structures. This is because the electric interactions between the two strands were shielded by water, and the hydrophobic effect dominated the interaction between the two strands. When an EEF >50 MV/cm was applied to the water cluster, the attractive force between the two strands in the parallel and antiparallel β sheet structures decreased and increased, respectively. Further, the binding affinity between the two strands in the parallel and antiparallel β sheet structures also decreased and increased, respectively. This is because the large EEF leads to dielectric saturation, and consequently reduces the effects of the dielectric shielding and hydrophobic interactions.

Nanosecond pulsed electric signals can affect electrostatic environment of proteins below the threshold of conformational effects: The case study of SOD1 with a molecular simulation study

“…To this regard, apart from few studies that have an experimental validation [56], the majority of the investigations are realized on the basis of molecular simulations. In particular, several endpoints have been explored using MD simulations [63–71] such as: the effects of external electric field on the stability of protein conformations [64–66], the stability of β-Sheets structures [69–71], the dependence of the field on the polarization of water molecules and the role of water in hydrophilic proteins, where in the interfacial gap, it forms an adhesive hydrogen-bond network between the interfaces, stabilizing early intermediates before native contacts are formed [72]. Almost all the papers reporting effects on the coupling of electric fields and proteins refer to intensities higher than 10 8 V/m [73–77], even in the case of recent papers giving contributions in comprehending the complete unfolding process of a protein [78].…”