Friday, May 10, 2013

No ice please

I’m not a fan of the Frank-Evans iceberg picture of hydrophobic hydration. But I will happily admit that, on the question of whether water hydrating small nonpolar solutes is more/less ordered and mobile than that in the bulk, the evidence is mixed. Nuno Galamba of the University of Lisbon now offers some more support for a weak version of the iceberg picture (J. Phys. Chem. B 117, 2153; 2013 – paper here). His MD simulations show that a subset of water molecules in the first hydration shell of methane have “significantly enhanced tetrahedrality and a slightly larger number of hydrogen bonds”, as well as slower reorientational dynamics, relative to the bulk. He adds that these characteristics should not be visible in the rdfs deduced from neutron scattering, explaining why they have not been seen experimentally. Whether this view extends to large hydrophobes is another matter, but these results at least argue for some small degree of water ‘ordering’, even if this is very far from ice-like.

The role of hydration water in the dynamics of hydrophobic sidechains of peptides is explored by Daniela Russo at the ILL in Grenoble and colleagues, using inelastic neutron scattering and simulations (J. Phys. Chem. B 117, 2829; 2013 – paper here). They say that the activation energy for methyl group motions increases with increasing level of hydration but eventually reaches a plateau when an extended hydrogen-bonding network is established around the group, which happens when it is essentially surrounded by a single layer of water. These sidechain dynamics seem to have a critical impact on the flexibility of the peptide as a whole, and so the degree of hydration appears to determine the onset of conformational freedom for the entire polypeptide.

Neeraj Sinha and colleagues at the Centre of Biomedical Magnetic Resonance in Lucknow have taken on the challenge of exploring water-protein interactions in a rather complex system, the helical coat protein of the filamentous virus Pf1 (R. N. Purusottam et al., J. Phys. Chem. B 117, 2837; 2013 – paper here). Using 2D proton-N15 NMR, they deduce that the filamentous assembly has a highly hydrated core which not only acts as a ‘glue’ but might also mediate the interaction of the arg44 residue with DNA.

Membrane transporters are membrane protein channels that pump directional transport of small molecules across the membrane, coupled to chemical energy sources in the cell. Their operation has generally been considered to involve a carefully orchestrated sequence of conformational changes to ensure one-way and selective transport. But it has been found that sometimes water and ions get through too, and the question arises of whether this is passive, osmotically driven ‘leakage’ or stoichiometric co-transport of these species. Emad Tajkhorshid and colleages at Illinois at Urbana investigate this question using MD simulations, for several classes of membrane transporters (J. Li et al., PNAS 110, 7696; 2013 – paper here). They find that these generally support states in which there are channels that permit passive water flux – but that this does not interfere with the coordinated vectorial transport of the primary substrate. Thus the transporters are imperfect, but not problematically so: as the authors put it, “Given the soft mechanical properties of transporter proteins, it comes as no surprise to observe harmless imperfections in the overall gating motions, which manifest themselves in the formation of water-conducting states. It would, of course, be a concern if these channels were large enough to leak the substrate, and/or long-lived to allow very large amounts of smaller species to permeate across the membrane. Neither of these aspects appears to be the observed in our results, because the leaky states are only large enough for small species such as water. Furthermore, it appears that these states only transiently rise during the transport cycle, an attribute that might make them difficult to capture experimentally.”

Solvation of small molecules in water has often been described using point charges affixed to the solutes to represent polarization effects. David Cerutti at Rutgers and colleagues present a quantum chemical approach for fitting such partial charges to solutes like amino acids (D. S. Cerutti et al., J. Phys. Chem. B 117, 2328; 2013 – paper here). They say that their approach, which represents an evolution from the simplest point-charge models of previous decades, predicts substantially more polarization of amino acids than earlier efforts using AMBER force fields.

More on urea-induced protein denaturation, this time from Michela Candotti of the Institute of Research in Biomedicine in Barcelona and colleagues, who use MD, SAXS and NMR data to develop an atomistic picture of the unfolded states and the energetics of unfolding and refolding (M. Candotti et al., PNAS 110, 5933; 2013 – paper here). They conclude that urea’s denaturing influence is a combination of kinetic (disrupting stabilizing intramolecular contacts) and thermodynamic (stabilizing the extended conformation) effects. As I understand it, the results support models based on direct interactions of urea and protein, while also revealing that the urea-unfolded state is rather different to the denatured conformation that exists in pure water.

Hydration is evidently important to DNA conformation, influencing the A-B transition, interactions with DNA-binding proteins, and perhaps even affecting shape in a sequence-dependent manner. There is some evidence that the hydration water of DNA has collective dynamics of a glassy nature, and this notion is offered further support in inelastic neutron scattering experiments by Alessandro Paciaroni at the Università degli Studi of Perugia and colleagues (A. Paciaroni et al., J. Phys. Chem. B 117, 2026; 2013 – paper here). They find that at 100 K the large-wavevector scattering from water, related to coherent excitations, seems to imply a character related to amorphous ice. In other words, the interactions with DNA significantly alter the structure and dynamics of the interfacial water.

Melittin, one of the multi-subunit peptides that seems to aggregate by dewetting, is a component of been venom that acts as an antimicrobial. The melittin tetramer forms a pore that inserts into lipid membranes, and Max Berkowitz and colleagues at UNC now suggest that its effect is to create transient water-permeable channels, making the membranes leaky (K. P. Santo et al., J. Phys. Chem. B 117, 5031; 2013 – paper here). The technique they use for MD simulations can handle timescales of up to microseconds, and they show that the melittin peptides gradually aggregate into a kind of wedge that punctures the membranes and allows water to pass through, before falling apart again.

[FeFe] hydrogenase catalyses hydrogen-ion reduction to gaseous hydrogen, and could therefore be a useful biocatalyst. Simulations by Martin McCullagh and Greg Voth at Chicago now show that it seems to work by coupling electron transfer to proton transfer along a previously unknown water channel accessing the active site (J. Phys. Chem. B 117, 4062; 2013 – paper here).

There are seemingly strange rumours that fully miscible liquids are inhomogeneous on length scales of hundreds of nanometres, a conclusion suggested by some light-scattering and small-angle neutron-scattering studies. For example, Marián Sedlák of the Slovak Academy of Sciences reported such a claim in a series of papers in 2006 (e.g. J. Phys. Chem. B 110, 4329). Could these be solute clusters, or perhaps nanobubbles stabilized by adsorbed solute? Sedlák and Dmytro Rak now investigate that latter possibility (J. Phys. Chem. B 117, 2495; 2013 – paper here). They look at a range of solutes: magnesium sulphate, citric acid, urea, and t-butyl alcohol, and find no significant differences in the scattering from normal and degassed solutions, apparently ruling out the nanobubble interpretation.