Evidence for Anomalous Hydration Dynamics near a Model Hydrophobic Peptide

Abstract

We present new quasi-elastic neutron scattering experiments and simulation analysis for studying the hydration water dynamics of N-acetyl-leucine-methylamide (NALMA) solutions as a function of concentration and temperature. The experiments show non-Arrhenius translational dynamics over the temperature range of -3 to +37 °C for all concentrations, and fits to the experimental intermediate scattering function show nonexponential relaxation dynamics. While the lower-concentration NALMA solution could be classified as an intermediate to strong liquid, the higher concentration is legitimately defined as a fragile liquid, and the hydration dynamics of the most concentrated solution exhibits very good correspondence with the same signatures of non-Arrhenius behavior and nonexponential dynamics as that observed for supercooled water well below -20 °C. The corresponding molecular dynamics simulation analysis of the high concentration data using the SPC water model, a common companion water model used in protein simulations, is severely limited in application to the dynamics of this system because of the very low temperature of maximum density of the SPC water model. However, the simulations are informative in the sense that nonexponential relaxation is still evident at the effectively higher temperatures, which indicates that the underlying potential energy surface is very rough at high concentrations, although the sampling is still sufficiently ergodic so that Arrhenius behavior is observed. We provide discussion in regards to the mutually beneficial connection between supercooled liquids and glasses and its biological importance for protein-water systems.

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

“…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.…”

“…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).…”

“…Table 1 lists the molar concentrations C, mass densities d, and water-to-solute molecular ratios, N W /N S , of the solutions under test. One can estimate from MD simulations for NALMA [24][25][26] that for complete hydration of NALA about 20-25 water molecules are needed. Thus, our investigations extend from a solvent/solute ratio of about 100:1, where there are enough water molecules to build up two or three hydration layers, to less than 10:1, where single water molecules or small water clusters are shared by several solute molecules.…”

“…Second, we searched for signatures of anomalous hydration dynamics such as non-exponential relaxation. For peptides such as NALA or NALMA, there is evidence for such anomalies from quasi-elastic neutron scattering and MD simulations, [25,26] and anomalous dynamics is also a well-known feature of protein solutions. [2,21] Finally, our results were expected to contribute to the understanding of the multimodal dielectric spectra of large biological molecules, such as proteins.…”