Drying-induced pore gating?

Morten Jensen and colleagues at D. E. Shaw Research in New York show using MD simulations of a potassium channel that hydrophobic gating – dewetting transitions in the hydrophobic pore interior – appear to be a viable mechanism for these and perhaps many other ion channels (M. Ø. Jensen et al., PNAS 107, 5833-5838; 2010 – paper here). This is one of the most persuasive cases I’ve seen for this very interesting possibility, building as it does on the full atomistic structure of the pore protein.

S. Khodadadi at Akron and colleagues have an interesting paper about the hydration of tRNA (Biophys. J. 98, 1321-1326; 2010 – paper here). They use neutron scattering and dielectric spectroscopy to measure the hydration dynamics of this molecule, and find that these are slower than those for typical proteins, but faster than DNA. This, they say, challenges the ‘slaving’ hypothesis, ‘which assumes that the dynamics of biological macromolecules just follows the dynamics of hydration water’. But is that really what it assumes? People have written various things about this, and I’d have to go back and check the papers they cite, but I’d not understood ‘slaving’ to mean something quite so simple – rather, it implies only that the dynamics of the solute and solvent are interdependent. Certainly, I don’t know that anyone would suggest the dynamics of hydration water are bulk-like and unaffected by the nature of the macromolecule. Still, interesting results.

As Thomas Elsaesser at the Max Born Institute in Berlin point out (L. Szyc et al., J. Phys. Chem. B 10.1021/jp101174q – paper here), the residence times of hydration water molecules around DNA actually show an analogously broad distribution to those around proteins, and fluctuations in the hydrogen-bond network happen on fast (fs to ps) timescales. They have looked at how vibrational energy pumped into the phosphate groups gets redistributed into DNA’s hydration shell, which acts as a heat sink. This happens quickly too: within a few fs, while energy transfer within the DNA molecule is slower (timescales around 20 ps).

Returning to proteins, Stefania Perticaroli and colleagues at Perugia find using depolarized light scattering that the water dynamics in dilute solutions of lysozyme display two distinct timescales: fast (>ps) bulk-like relaxation, and slow (a few ps) due to hydration water (S. Perticaroli et al., J. Phys. Chem. B 10.1021/jp101896f – paper here).

One possible mechanism for the operation of antifreeze proteins is to bind to the surface of ice crystallites and stop them growing further. According to Knight and DeVries, this should also imply that the AFP’s should inhibit the melting of ice. Yeliz Celik at Ohio University and colleagues have presented experimental evidence for this (PNAS 107, 5423-5428; 2010 – paper here). They find that ice can be superheated up to 0.44 C in AFP solutions.

Does the electric field at a charged surface induce an ice-like hydrogen-bonding pattern in water? No, accortding to Tahei Tahara and colleagues at RIKEN’s Advanced Science Institute in Saitama, Japan (S. Nihonyanago et al., JACS 132, 6867-6869; 2010 – paper here). They use a form of vibrational sum frequency generation spectroscopy to look at the water structure in the Gouy-Chapman layer at the surface of a charged lipid monolayer, and say that it looks bulk-like.

Well, by this measure perhaps. But FT-IR and DSC measurements of water confined between lamellar bilayers of AOT surfactant suggest that the water here has three components: some is bulk-like, some closely linked to the surfactant head groups, and a layer about 0.5 nm between the two where the bulk H-bond network is disrupted (E. Prouzet et al., J. Phys. Chem. B 10.1021/jp101176v – paper here).

Another nice example of water in the active site playing a key role in enzymatic activity: Karol Kaszuba at the Tampere University of Technology in Finland and colleagues say that water in the binding site enables the high stereoselectivity of a beta-adrenergic receptor, a potential target for beta-blockers, by mediating H-bonding interactions between different enantiomers of the beta-blocker nebivolol (K. Kaszuba et al., J. Phys. Chem. B 10.1021/jp909971f – paper here).

Many simulations have shown single-file filling of and transport through carbon nanotubes. Now Wim Wenseleers and colleagues at Antwerp claim to have seen this experimentally for the first time (S. Cambré et al., Phys. Rev. Lett. 104, 207401; 2010 – paper here). They see the signature of such behaviour in the splitting of a Raman mode, for nanotubes of diameters down to 0.548 nm. But interestingly, the details of the filling (as revealed by the Raman shift) shows a complex, non-monotonic dependence on diameter, owing to variations in tube chirality.

Martina Havenith at Bochum and her coworkers have been using THz spectroscopy to reveal some interesting new features of hydration. Now she, Dominik Marx and their colleagues have used MD simulations to figure out precisely what manner of intermolecular motions are being probed by this technique (M. Heyden et al., PNAS 10.1073/pnas.0914885107 – not yet online). They conclude that ‘a modification of the hydrogen-bond network, e.g. due to the presence of a solute, is expected to affect vibrational motion and THz absorption intensity at least on a length scale that corresponds to two layers of solvating water molecules’ – and that this spectroscopy particularly probes strongly correlated molecular motions.

Here’s something that should stir up discussion: J. Raúl Grigera and Andres McCarthy in Argentina have conducted MD simulations of the pressure induced denaturation of proteins such as lysozyme and apomyoglobin, and say that they think the unfolding is caused by weakening of hydrophobic interactions owing to a change in water structure (weakening of the H-bonding network) (Biophys. J. 98, 1626-1631; 2010 – paper here). Other studies have tended to emphasize the penetration of water into the hydrophobic interior. Besides my now almost knee-jerk suspicion of explanations invoking ‘water structure’, I am forced to wonder, first, if such changes would be profound enough at the kbar pressures used here, and second, to what extent the hydrophobic interaction is really dependent on the H-bond network as opposed to being a more general solvophobic effect.

Nanobubbles – ah, one day I hope to bring together the various and diverse findings reported about their behaviour. In some studies (e.g. Jin et al., J. Phys. Chem. B 111, 2255; 2007), it has been claimed that nanobubbles will form in mixtures of non-aqueous solvents (that have some amphiphilic properties) with water. That notion is investigated by Xuehua Zhang and coworkers at the University of Melbourne (A. Häbich et al., J. Phys. Chem. B 114, 6962-6967; 2010 – paper here). They find that the behaviour of such mixtures is inconsistent with light scattering by bubbles (for example, there is no change in scattering on degassing), and they attribute the scattering instead to the presence of impurities.

Microbubbles are the focus of a study by Derek Chan, also at Melbourne, and colleagues (I. U. Vakarelski et al., PNAS 10.1073/pnas.1005937107; paper here). They use AFM measurements to look at the factors that influence bubble coalescence, particularly the hydrodynamic interactions between microbubbles. Curiously, they say that the hydrodynamics can induce a dynamic coalescence mode which operates as two bubbles separate.

Going back to January, Jan Swenson and colleagues at Chalmers University of Technology in Sweden claim to have identified a slow relaxation process in water (four orders of magnitude slower than the normal viscosity-related relaxation) due to collective motions of the hydrogen-bonded network (H. Jansson et al., Phys. Rev. Lett. 104, 017802; 2010 – paper here). They say that this type of relaxation has been identified before in mono- and polyalcohols, such as glycerol (R. Bergman et al., J. Chem. Phys. 132, 044504; 2010). The researchers see it in water in measurements of the dielectric response. They can’t really say much yet about what causes it, although the suggested connection to the ‘chain-like’ structures proposed by Huang et al. (PNAS 106, 15214; 2009) is speculative in the extreme.

See also Jan’s recent paper with José Teixeira (J. Chem. Phys. 132, 014508; 2010 – paper here) on the relaxation behaviour of supercooled water through the no-man’s-land between 150 and 235 K. They propose a crossover between cooperative α-relaxation at higher temperatures and ‘local’ β-relaxation at low temperatures.

Also, I don’t believe I mentioned previously a paper by Alenka Luzar and colleagues published last November (Phys. Rev. Lett. 103, 207801; 2009 – paper here) on the dynamics of alignment of a hydrated nanoparticle in an electric field. This process is important for applications such as dielectrophoresis and the electrical control of optical properties. Using MD simulations, the researchers conclude that the torque exerted by a typical experimentally realizable field strength is greater than kT (so alignment is possible even at the nanoscale) and greater than that estimated using continuum methods. Moreover, the alignment times are fast – of the order of a few hundred picoseconds.

Greg Voth and colleagues run a check on the self-consistent charge density functional tight binding (SCC-DFTB) method that has been used for quantum simulations of water in various systems, including some biological ones (C. M. Maupin et al., J. Phys. Chem. B 114, 6922-6931; 2010 – paper here). They look at what the method predicts for hydrated protons, and find that it puts the excess proton in a Zundel ion (H5O2+) in the resting state – unlike some other quantum chemical methods, and in contrast to what experiments have suggested. This presumably raises questions about the validity of the method.

Brad Bauer and Sandeep Patel at the University of Delaware also present a kind of model validation study for different water potentials, looking at how these affect the hydrophobic attraction of two flat plates (J. Phys. Chem. B 10.1021/jp101995d – paper here). They find that while many of the structural and dynamic aspects are the same for all the potentials studied – average density, fluctuations, hydrogen bonding – the potential of mean force for attraction between the plates is reduced when the water is polarizable.

Another validation study for simulations of biomolecules is described by Klaus Liedl at Innsbruck and colleagues (J. Phys. Chem. B 114, 7405; 2010 – paper here). They look at how simulations of the X-ray structure of the protein fXa, a key enzyme in blood coagulation, are affected by different choices of sets of water molecules in the hydration sphere. They conclude that only by judicious placement of water molecules around the protein, using available crystal structure data, will ensure a reasonable sampling of phase space when studying the protein’s dynamics. Otherwise, the simulations may take an unfeasible time for the hydration environment to equilibrate. One can’t, apparently, just plunge the protein into a bulk-like solvent environment and assume that it’ll find its own way to the right hydration structure.

A few more to come, but this is enough for now.

Two announcements of publications:
There is a special volume of the Journal of Electron Spectroscopy and Related Phenomena (177 (2-3), March 2010) devoted to water and hydrogen bonds investigated through inner-shell spectroscopies.
And the long-overdue collection of papers stemming from a conference on ‘water and life’ in Varenna in 2005 is now out:
Water and Life: The Unique Properties of H2O, eds Lynden-Bell, Ruth M., Conway Morris, Simon, Barrow, John D.,Finney, John L., and Harper, Charles L., Jr. Boca Raton, Florida: CRC Press / Taylor & Francis Group, 2010. More details here. I just received my copy, and it looks still relevant despite the long delay in publication.