Memory-kernel extraction for different molecular solutes in solvents of varying viscosity in confinement.

The friction coefficient of molecular solutes depends on the solute, on the solvent, and on the solute-solvent interactions, but is typically assumed to not depend on an externally applied force that acts on the solute. In this paper we compute the friction memory function from molecular dynamics simulations and show that the friction coefficients of harmonically confined methane, water, Na^{+}, an artificial Na^{-} ion, and glycerol in water in fact increase with confinement strength. The results show that the friction increase with confinement strength is a fundamental effect that occurs for hydrophobic, hydrophilic, as well as charged molecules. We demonstrate that a parameter-free extraction of the running integral over the memory function yields the most robust results when compared to methods based on parametrization or Fourier transforms. In all systems, this friction increase is accompanied by a slowdown of the solvent dynamics in the first hydration shell of the solutes. By simulations of a confined glycerol molecule in water-glycerol mixtures, we furthermore demonstrate that the friction dependence on the confining potential is magnified in more viscous solvents, which suggests that this effect plays an important role for larger molecules in highly viscous solutions like polymer melts, in line with dynamic scaling arguments.

Impact of secondary structure and hydration water on the dielectric spectrum of poly-alanine and possible relation to the debate on slaved versus slaving water.

Using extensive molecular dynamics simulations of a single eight-residue alanine polypeptide in explicit water, we investigate the influence of α-helix formation on the dielectric spectrum. For this, we project long equilibrium trajectories into folded and unfolded states and thereby obtain dielectric spectra representative for disordered as well α-helical conformations without the need to change any other system parameter such as pH or temperature. The absorption spectrum in the α-helical state exhibits a feature in the sub-GHz range that is significantly stronger than in the unfolded state. As we show by an additional decomposition into peptide and water contributions, this slow dielectric mode, the relaxation time of which matches the independently determined peptide rotational relaxation time, is mostly caused by peptide polarization correlations, but also contains considerable contributions from peptide-water correlations. In contrast, the peptide spectral contribution shows no features in the GHz range where bulk water absorbs, not even in the peptide-water correlation part, we conclude that hydration water around Ala8 is more influenced by peptide polarization relaxation effects than the other way around. A further decomposition into water-self and water-collective polarization correlations shows that the dielectric response of hydration water is, in contrast to electrolyte solutions, retarded and that this retardation is mostly due to collective effects, the self relaxation of hydration water molecules is only slightly slowed down compared to bulk water. We find the dynamic peptide-water polarization cross correlations to be rather long-ranged and to extend more than one nanometer away from the peptide-water interface into the water hydration shell, in qualitative agreement with previous simulation studies and recent THz absorption experiments.

Unfolding and folding internal friction of ß-hairpins is smaller than that of α-helices.

By the forced unfolding of polyglutamine and polyalanine homopeptides in competing α-helix and ß-hairpin secondary structures, we disentangle equilibrium free energetics from nonequilibrium dissipative effects. We find that α-helices are characterized by larger friction or dissipation upon unfolding, regardless of whether they are free energetically preferred over ß-hairpins or not. Our analysis, based on MD simulations for atomistic peptide models with explicit water, suggests that this difference is related to the internal friction and mostly caused by the different number of intrapeptide hydrogen bonds in the α-helix and ß-hairpin states.

Peptide chain dynamics in light and heavy water: zooming in on internal friction.

Frictional effects due to the chain itself, rather than the solvent, may have a significant effect on protein dynamics. Experimentally, such "internal friction" has been investigated by studying folding or binding kinetics at varying solvent viscosity; however, the molecular origin of these effects is hard to pinpoint. We consider the kinetics of disordered glycine-serine and α-helix forming alanine peptides and a coarse-grained protein folding model in explicit-solvent molecular dynamics simulations. By varying the solvent mass over more than two orders of magnitude, we alter only the solvent viscosity and not the folding free energy. Folding dynamics at the near-vanishing solvent viscosities accessible by this approach suggests that solvent and internal friction effects are intrinsically entangled. This finding is rationalized by calculation of the polymer end-to-end distance dynamics from a Rouse model that includes internal friction. An analysis of the friction profile along different reaction coordinates, extracted from the simulation data, demonstrates that internal as well as solvent friction varies substantially along the folding pathways and furthermore suggests a connection between friction and the formation of hydrogen bonds upon folding.

Electrolytes in a nanometer slab-confinement: ion-specific structure and solvation forces.

We study the liquid structure and solvation forces of dense monovalent electrolytes (LiCl, NaCl, CsCl, and NaI) in a nanometer slab-confinement by explicit-water molecular dynamics (MD) simulations, implicit-water Monte Carlo (MC) simulations, and modified Poisson-Boltzmann (PB) theories. In order to consistently coarse-grain and to account for specific hydration effects in the implicit methods, realistic ion-ion and ion-surface pair potentials have been derived from infinite-dilution MD simulations. The electrolyte structure calculated from MC simulations is in good agreement with the corresponding MD simulations, thereby validating the coarse-graining approach. The agreement improves if a realistic, MD-derived dielectric constant is employed, which partially corrects for (water-mediated) many-body effects. Further analysis of the ionic structure and solvation pressure demonstrates that nonlocal extensions to PB (NPB) perform well for a wide parameter range when compared to MC simulations, whereas all local extensions mostly fail. A Barker-Henderson mapping of the ions onto a charged, asymmetric, and nonadditive binary hard-sphere mixture shows that the strength of structural correlations is strongly related to the magnitude and sign of the salt-specific nonadditivity. Furthermore, a grand canonical NPB analysis shows that the Donnan effect is dominated by steric correlations, whereas solvation forces and overcharging effects are mainly governed by ion-surface interactions. However, steric corrections to solvation forces are strongly repulsive for high concentrations and low surface charges, while overcharging can also be triggered by steric interactions in strongly correlated systems. Generally, we find that ion-surface and ion-ion correlations are strongly coupled and that coarse-grained methods should include both, the latter nonlocally and nonadditive (as given by our specific ionic diameters), when studying electrolytes in highly inhomogeneous situations.

Ion-specific excluded-volume correlations and solvation forces.

Realistic ion-ion and ion-surface potentials from explicit-water simulations are used in implicit-solvent Monte Carlo simulations to study the ionic structure and double-layer forces in a nanometer slab confinement. The highly salt-specific results can be reproduced and rationalized by a simple nonlocal Poisson-Boltzmann theory of a nonadditive primitive model, in which effective hard-sphere radii are obtained from the short-ranged part of the pair potentials. Steric corrections to solvation forces are mainly repulsive and strongly coupled to the ion-surface interactions.