Wednesday, May 6, 2009

Catching up

I have been on travel and caught up with numerous other things for several weeks, which not only means I have been unable to post but also that I’ve doubtless missed some interesting things over the recent period. If so, apologies for that – and feel free to let me know! But note also that my email address at Nature won’t be active for much longer, as I am very shortly leaving my role there as a writer – I’m no longer able to keep that going alongside the other demands on my time. I will no doubt keep writing occasionally for Nature nonetheless, but will be henceforth reachable at

To business, and in no particular order from the stack of papers in my pile…

Martina Havenith and her coworkers at Bochum have continued their highly revealing work on hydration structures using terahertz spectroscopy. In a new paper (B. Born et al., JACS 131, 3752 (2009) – paper here) they look at the hydration networks around various small peptides at low hydration levels, and find that the collective motions of peptide + solvent that seem to characterize protein hydration shells disappear below a minimum number of hydration waters, which appears to be well below that required for monolayer coverage.

This issue of solvent-protein dynamical correlations is also studied by Nigel Scrutton and colleagues at the University of Manchester (D.J. Heyes et al., Angew. Chem. Int. Ed. 48, 3850; 2009 – paper here). They find that proton tunnelling in protochlorophyllide oxireductase, a light-driven enzyme involved in chlorophyll biosynthesis, requires protein motions that appear to be slaved to the solvent, whereas hydride transfer in this species does not. It seems significant that proton, but not hydride, transfer occurs only close to the protein’s glass transition temperature, when the protein-solvent coupling is likely to be most acute.

In my recent ChemPhysChem paper (here), I referred to some recent work on denaturants by Jeremy England and coworkers, inadvertently describing it as though it came out of Vijay Pande’s lab (J. L. England, V. S. Pande & G. Haran, JACS 130, 11854; 2008). Actually I gather it was done mostly at the lab of Gilad Haran at the Weizmann Institute in Israel. Apologies for that oversight. Gilad has told me of his recent work on protein collapse using single-molecule FRET (G. Ziv & G. Haran, JACS 131, 2942; 2009 – paper here; and G. Ziv et al., Phys. Chem. Chem. Phys. 11, 83; 2009 – paper here). The former paper argues that the action of denaturants operates primarily by modulating the collapse of the denatured state, rather than acting on the transition from molten globule to folded state.

A recent special issue of J. Phys. Chem. B on aqueous solutions and interfaces (113(13)) has given me a lot to catch up with. Sotiris Xantheas and Greg Voth give a nice overview here. Among the interesting papers therein, Greg profiles the case for the amphiphilic nature of the hydrated proton at the interface with hydrophobic media (S. Iuchi et al., J. Phys. Chem. B 113, 4017; 2009 – paper here); Janamejaya Chowdhary and Branka Ladanyi use MD to investigate the dynamics of hydrogen-bond making and breaking (113, 4045; 2009 – paper here), and Yves Rezus and Huib Bakker use femtosecond IR spectroscopy to look at how various amphiliphilic small molecules alter water structure in the bulk (113, 4038; 2009 – paper here). Rezus and Bakker find that trimethylamine-N-oxide seems to be special in the latter regard, increasing the rate of reorientation of mobile water, which might be interpreted as a sign that it increases the number of defects in the H-bonded network.

On much the same topic, Greg Voth and colleagues have used MD to look at the interactions of hydrophobic, nonpolar solvents in aqueous salt (NaCl) and acid (HCl) solution (H. Chen et al., J. Phys. Chem. B ASAP; paper here). They find unusual solvated-proton structures in the acid which are bound to the hydrophobes, again supporting the idea that the hydrated protons act as amphiphiles. This might explain why protons seem anomalous in the Hofmeister series. And Michael Brindza and Robert Walker at the University of Maryland use SHG to look at solvation mechanisms of small molecules (p-nitroanisole, indoline) at the interface of polar solids and various liquids, offering a broader context for understanding what water in particular does in such cases (JACS 131, 6207; 2009 – paper here). Alenka Luzar and her coworkers have used MD to look at the solvation of monosodium glutamate, making a comparison to experimental data on this system (C. D. Daub et al., J. Phys. Chem. B ASAP; paper here). On the whole the agreement is good with the neutron-diffraction data, but there are some important differences – for example, the simulations couldn’t reproduce the experimentally observed reduction in water-water correlations – that presumably point to inadequacies of using classical potentials. (Incidentally, my spellchecker tirelessly insists that ‘solvation’ should be ‘salvation’ – forgive me if I don’t fail to catch them all…)

Alenka’s comparison with experiment here relies heavily on Alan Soper’s neutron data and its analysis using empirical potential structure refinement, which was conducted for those data by Alan with Sylvia McLain and Anthony Watts. Sylvia has sent me a paper in which she, with Soper and Watts alongside Jeremy Smith and Isabella Daidone, use this same technique to deduce the nature of hydration and interaction between various amino acid dimmers (S. E. McLain et al., Angew. Chem. Int. Ed. 47, 9059; 2008 – paper here). This is extremely interesting, as it challenges the conventional view that the main driving force for association is the interaction of hydrophobic regions. In contrast, this study finds that it is the charged sites on the peptides that dominate the association, and that interaction decreases as hydrophobicity increases. Could the same apply in protein folding itself?

Sason Shaik and his collaborators have now published the full analysis of the role on internal waters in the action of cytochrome P450 StaP (Y. Wang et al., JACS ASAP; 2009 – paper here), the preliminary account of which I discussed in my CPC paper.

Anders Nilsson, Lars Pettersson and their coworkers have now published the work that I referred to in a Nature article last year, in which they challenge the view that X-ray and neutron diffraction data uniquely support the conventional tetrahedral-coordinate picture of water structure (K. T. Wikfeldt et al., J. Phys. Chem. B 113, 6246; 2009 – paper here). Needless to say, this remains highly controversial stuff.

Pedro de Pablo and colleagues at Madrid have reported some very striking results on the desiccation of viruses. They say that drying of two different viruses causes the ejection of DNA and, in one case, collapse of the remaining capsid owing to capillary forces of the water menisci inside (C. Carrasco et al., PNAS 106, 5475; 2009 – paper here).

A couple more papers on nanoconfined water, in hydrophobic but less explicitly biological environments. Sow-Hsin Chen and colleagues say that supercooled water, which shows a density minimum under confinement in hydrophilic mesoporous materials, has none such in a hydrophobic material (Y. Zhang et al., J. Phys. Chem. B ASAP: paper here). And Gene Stanley and colleagues look at the H-bond dynamics of TIP5P water in a hydrophobic nanopore slit (S. Han et al., Phys. Rev. E 79, 041202; 2009 – paper here). They say that the H-bonds are shorter-lived in this case than in the bulk, and the relaxation time is smaller, but the general qualitative behaviour is much the same (e.g. the temperature-dependence of the average H-bond lifetime, and non-exponential lifetime distributions).

Ahmed Zewail and Ding-Shyue Yang recently reported ultrafast electron crystallography of water at low temperatures (c. 150 K) at the surface of graphite (PNAS 106, 4122; 2009 – paper here). It’s not strictly relevant to water in biology, perhaps, but an issue that I’ve started to follow increasingly and which touches on water’s general ability to order at interfaces. The results imply that, perhaps contrary to expectation (especially when compared with hydrophobic H-terminated silicon), this hydrophobic surface doesn’t disrupt a highly ordered interfacial structure. It seems this may be because the graphite surface is stepped, which apparently allows it to template a cubic-ice structure.

I recently wrote a column for Nature Materials (8, 250; 2009 – see here) on hydrophobicity at larger scales than the molecular, and in particular on the discussions of wetting by water of nano- and microstructured surfaces via Wenzel or Cassie states. This is relevant to biology insofar as it bears on the question of wettability of, e.g. insect legs and lotus leaves. There is a nice recent simulation paper on the topic by Takahiro Koishi at the University of Fukui and colleagues (PNAS doi:10.1073/pnas.0902027106 – not yet online), which describes the different conditions (of surface topology and so forth) under which Wenzel and Cassie wetting exist, and the possibility of their coexistence. And Abraham Marmur has flagged up his paper from last year (Langmuir 24, 7573; 2008 – paper here) in which he too looks at general geometric considerations that might promote such high-contact-angle states.

Here’s an intriguing thing that had escaped my notice until now: it seems that voltages may be generated in carbon nanotubes along the tube axis when water flows through them (see S. Ghosh et al., Science 299, 1042; 2003 – paper here). That’s suggestive from the perspective that views nanotubes as simple analogues of hydrophobic protein channels. Already it seems that this idea has been explored for power conversion (Y. C. Zhao et al., Adv. Mater. 20, 1772; 2008). Now Quanzi Yuan and Ya-Pu Zhao of the Institute of Mechanics in Beijing offer an explanation for the phenomenon in terms of the alignment of water molecules in the hydrogen-bonded chain within the nanotube (JACS ASAP; paper here).

More on this general topic from Bo Liu at the Graduate University of the Chinese Academy of Sciences in Beijing and coworkers, who describe simulations of a model system in which end-functionalized short carbon nanotubes are embedded in a phospholipid bilayer as mimics of aquaporin (B. Liu et al., Nano Lett. 9, 1386; 2009 – paper here). Two charges are placed near the tube midpoints, to simulate the NPA region of aquaporin where water selectivity and proton gating is thought to happen. But proton conduction couldn’t be studied explicitly in these classical MD simulations. That aside, the device seems to work more or less as planned, in theory. But can we make it?

Well, that’s not the end of it, but my desk looks a whole lot better.