Folding of Gas-Phase Polyalanines in a Static Electric Field: Alignment, Deformations, and Polarization Effects

Abstract

Monte Carlo simulations of the temperature-induced unfolding of small gas-phase polyalanines in a static, homogeneous electric field are reported, based on the AMBER ff96 force field. The peptides exhibit a structural transition from the native alpha-helix state to entropically favored beta-sheet conformations, before eventually turning to extended coil at higher temperatures. Upon switching the electric field, the molecules undergo preferential alignment of their dipole moment vector toward the field axis and a shift of the alpha-beta transition to higher temperatures. At higher field strengths (>10(8) V/m) the molecules stretch and the alpha-beta and beta-coil transitions merge. A simple three-state model is shown to account for the observed behavior. Under even higher fields, density functional theory calculations and a polarizable force field both show that electronic rearrangements tend to further increase the dipole moment, polarization effects being approximately half in magnitude with respect to stretching effect. Finally a tentative (temperature, field-strength) phase diagram is sketched.

Hydrogen bond perturbation in hen egg white lysozyme by external electromagnetic fields: A nonequilibrium molecular dynamics study

“…9 Although such field intensities are several orders of magnitude larger than those applied experimentally or industrially, 5 it is necessary to apply field intensities greater than circa 0.01 V Å −1 to observe tangible effects for solvated proteins within the limited time scales amenable to molecular simulation. 9,10 Our results are similar to those of the group of Yarovsky, 11 where both static and oscillating (from 1.225 to 4.9 GHz) electric fields were applied to insulin chain-B, and the insulin chain-A-chain-B complex. a) Current address: Department of Biophysical Chemistry, Lund University, Sweden.…”

“…In our previous work, 9 an rms intensity of 0.01 V/Å led to statistically indistinguishable changes in the HEWL mutants' RMSD's or gross dipolar alignments over 25 ns vis-à-vis zero-field conditions in either static or 2.45 GHz e/m fields; this observation is in accord with gas-phase simulations of polyalinines in static 0.01 V/Å electric fields performed by Calvo and Dugourd. 10 Indeed, previous analysis 9 has indicated that rms intensity exhibits a linear type response to dipole alignment; a behavior we would also expect in the current analysis. The external fields were applied in conjunction with NPT coupling, and are referred to as nonequilibrium NVT (NNPT) simulations.…”

Electric Field as a Disaggregating Agent for Amyloid Fibrils

“…Second, we employed fixed-charge model for the peptide's force-field, which neglects the effect of electronic polarization due to the electric field. 60 Third, the effect of the electric field on water was neglected. Since water mediates interactions among peptide atoms, this effect may prove to be important.…”

Effects of external electromagnetic fields on the conformational sampling of a short alanine peptide

“…[8, 9] A lower r.m.s. intensity field of 0.01 V/Å was also used to validate that essentially no field effects were observed within the timescales of the simulation, as found in previous studies,[8, 9, 13] and this determined to be the case here.…”

“…[2–6] Bearing this in mind, molecular simulation provides one possible avenue for the unambiguous study of such effects. Recent work in this group,[7–9] as well as others,[10–14] has examined the athermal effects of electric and e/m fields on the structural stability of several enzymes and peptides. The hen egg white lysozyme (HEWL) simulations demonstrated the good stability of the enzyme across a range of field strengths and frequencies with field strengths in the region of 0.05 V/Å or greater required to disrupt the secondary structure of the protein (via perturbation of intra‐protein hydrogen bonds).…”