Protein orientation in time-dependent electric fields: orientation before destruction

Abstract

Proteins often have nonzero electric dipole moments, making them interact with external electric fields and offering a means for controlling their orientation. One application that is known to benefit from orientation control is single-particle imaging with x-ray free-electron lasers, in which diffraction is recorded from proteins in the gas phase to determine their structures. To this point, theoretical investigations into this phenomenon have assumed that the field experienced by the proteins is constant or a perfect step function, whereas any real-world pulse will be smooth. Here, we explore the possibility of orienting gasphase proteins using time-dependent electric fields. We performed ab initio simulations to estimate the field strength required to break protein bonds, with 45 V/nm as a breaking point value. We then simulated ubiquitin in time-dependent electric fields using classical molecular dynamics. The minimal field strength required for orientation within 10 ns was on the order of 0.5 V/nm. Although high fields can be destructive for the structure, the structures in our simulations were preserved until orientation was achieved regardless of field strength, a principle we denote ''orientation before destruction.''

Electric Field Effect on Inhibiting the Co-fibrillation of Amyloid Peptides by Modulating the Aggregation Pathway

“…Further, with the strongly affected dipole moment under high EF intensity (≥20 mV/nm), these peptides would arrange along the EF direction with a decreased interaction between themselves. These results were in line with the previous study that the dramatic rearrangement of the structure results in a strong residual force on charged sites in the protein, leading to an intense disruption of β-sheet secondary structure and inhibition of fibrillation.…”

“…43 Moreover, the direction and intensity of the dipole moment can well reflect the stability of the overall system composed of peptides or proteins. 53,54 In the case of 0 mV/nm, the two pentamers showed opposite contributions of dipole moment in the X and Y directions (Figure 6B). Similar behavior existed when EF intensities of 0.2 and 2 mV/nm were applied (Figures 6C and S9A).…”

Stability and conformational memory of electrosprayed and rehydrated bacteriophage MS2 virus coat proteins

“…The comparison of the stability of simulated proteins in vacuum using different force fields indicated a minimal influence of the choice of force field on the protein stability ( Marklund et al., 2009 ). Hence, as in our previous studies ( Sinelnikova et al., 2021 ; Marklund et al., 2009 , 2017 ; Patriksson et al., 2007 ; Mandl et al., 2020 ), the OPLS-AA force field was utilized to estimate the forces between the atoms ( Kaminski et al., 2001 ) with applied virtual sites ( Feenstra et al., 1999 ). The protein structures were placed under periodic boundary conditions in a dodecahedral box.…”

Electromagnetic bioeffects: a multiscale molecular simulation perspective

“…The complementarity of quantum and classical theory simulation methods was recently demonstrated in the possibility to orient gas-phase proteins such as ubiquitin using time-dependent EF. 165 The ab initio simulations were used to estimate the field strength required to break protein bonds, with 45 V nm −1 as a breaking point value while the MD simulations showed the minimal field strength required for orientation within 10 ns to be on the order of 0.5 V nm −1 . Although high fields can be destructive for proteins, the structures in these simulations were preserved until orientation was achieved regardless of field strength, a principle the authors denoted as “orientation before destruction.” Following this study, Sinelnikova et al identified the unfolding pathways of ubiquitin, induced by experimentally achievable external electric fields.…”