Dielectric Relaxation of Aqueous Solutions of Hydrophilic versus Amphiphilic Peptides

Abstract

We report on molecular dynamics simulations of the frequency-dependent dielectric relaxation spectra at room temperature for aqueous solutions of a hydrophilic peptide and an amphiphilic peptide at two concentrations. We find that only the high-concentration amphiphilic peptide solution exhibits an anomalous dielectric increment over that of pure water, while the hydrophilic peptide exhibits a significant dielectric decrement. The dielectric component analysis carried out by decomposing these peptide solutions into peptide, hydration layer, and outer layer(s) of water clearly shows the presence of a unique dipolar component with a relaxation time scale on the order of approximately 25 ps (compared to the bulk water time scale of approximately 11 ps) that originates from the interaction between the hydration layer water and the outer layer(s) of water. Results obtained from the dielectric component analysis further show the emergence of a distinct and much lower frequency relaxation process for the high-concentration amphiphilic peptide compared to the hydrophilic peptide due to strong peptide dipolar couplings to all constituents, accompanied by a slowing of the structural relaxation in all water layers, giving rise to time scales close to approximately 1 ns. We suggest that the molecular origin of the dielectric relaxation anomalies is due to frustration in the water network arising from the amphiphilic chemistry of the peptide that does not allow it to reorient on the picosecond time scale of bulk water motions. This explanation is consistent with the idea of the "slaving" of residue side chain motions to protein surface water, and furthermore offers the possibility that the anomalous dynamics observed from a number of spectroscopies arises at the interface of hydrophobic and hydrophilic domains on the protein surface.

Hydration Dynamics of Water near an Amphiphilic Model Peptide at Low Hydration Levels: A Dielectric Relaxation Study

“…NALA and NALMA are sufficiently similar to exploit the simulation results in our data analysis. In agreement with the simulations, [29] our experiments exhibit an apparently monomodal structure of the dielectric spectrum at C = 0.5 m, which at 2 m turns into a bimodal structure. However, the simulations do not reveal the KWW-type broadenings observed experimentally, so that the two-peak structure of the simulated spectrum is better resolved than that observed experimentally.…”

“…For multimodal spectra such procedures can be cumbersome, especially if the number of modes and appropriate form of the relaxation function is unknown. [32] While existing studies of the hydration dynamics of model peptides by other techniques give evidence for stretched exponential behaviour, [24][25][26][27][28][29] the suitability for describing the dynamical processes driving di-A C H T U N G T R E N N U N G electric relaxation did not seem to be guaranteed a priori.…”

“…[16] The utility of this formalism for understanding experimental dielectric spectra of aqueous solutions has been shown in our recent studies of proteins [17,18] and saccharides. [30] Murarka and Head-Gordon [29] have used this formalism to analyse the simulated dielectric spectrum of NALMA. NALA and NALMA are sufficiently similar to exploit the simulation results in our data analysis.…”

“…Simulations indicate that hydration dynamics depends on the closest amino acid, [22,23] but this specificity is difficult to verify for real systems because the experiments map averages over individual amino acid-water interactions. Head-Gordon and co-workers [24][25][26][27][28][29] have pointed out that some basic features of hydration dynamics may be assessed by studying simple model peptides.…”

“…Herein, we follow the strategy of Head-Gordon and co-workers [24][25][26][27][28][29] and resort to a simple model peptide. Specifically, we focus on the amphiphilic model peptide N-acetyl-leucine amide (NALA), in which a hydrophobic side chain is attached to a blocked polypeptide backbone (Scheme 1).…”