Hydration dynamics, amyloids, and more

My pile of water-related papers is stacking up worryingly, so let me now try to clear it. Thanks again to everyone who has sent me papers – it is always a pleasure to receive them.

Roberto Senesi and Antonino Pietropaolo at Rome and their colleagues have been producing a succession of papers in which they use inelastic neutron scattering to study the momentum distributions of protons in water in a variety of settings: in nano-confined systems (G. Reiter et al., Phys. Rev. Lett. 97, 247801; 2006 – paper here; and V. Garbuio et al., J. Chem. Phys. 127, 154501; 2007 – paper here), in supercooled water (A. Pietropaolo et al., Phys. Rev. Lett. 100, 127802; 2008 – paper here) and the ambient liquid and supercritical phase (C. Pantalei et al., Phys. Rev. Lett. 100, 177801; 2008 – paper here), and in a protein hydration shell (R. Senesi & A. Pietropaolo, Phys. Rev. Lett. 98, 138102; 2007 – paper here). The last of these is of course particularly relevant here. The authors study the momentum distributions for hydration protons around lysozyme both above (290 K) and below (180 K) the dynamical transition at around 220 K. At 290 K, the results are consistent with a hydration shell that is slightly denser than bulk water, with a smaller oxygen-oxygen distance that confines the protons in a double well, with the possibility of tunnelling between minima. This suggests that tunnelling may occur even at room temperature ion the hydration shell, with potential implications for biological function. That, of course, is something that would be picked up in simulations only in a full quantum-chemical treatment.

There’s an important paper by Johan Qvist and Bertil Halle in JACS (doi:10.1021/ja802668w paper here) on rotational dynamics of water in hydrophobic hydration shells, probed by deuterium NMR. They find for four partly hydrophobic solutes, including two peptides and two osmolytes, that below 255 K hydration water rotates with a lower activation energy, and faster if the temperature is low enough, than it does in the bulk. As they say, “these findings reverse the classical ‘iceberg’ view of hydrophobic hydration by indicating that hydrophobic hydration water is less ice-like than bulk water.” It will be good to put that idea finally to rest. Moreover, the two osmolytes have opposite effects on protein stability but the same effect on water dynamics, again challenging the common view that somehow ‘water structure’ is responsible for these effects. As the authors say, “Such poetic explanations may be misleading unless they are accompanied by a precise definition of water structure. Indeed, much of the confusion in the literature stems from indiscriminate use of the word ‘structure’. Furthermore, the connection between water dynamics and structure is non-trivial.” These NMR results do, however, seem to conflict with quasi-elastic neutron scattering studies (e.g. D. Russo et al., Biophys. J. 86, 1852; 2004), and Qvist and Halle suggest some reasons for that. A final word of caution: the small peptides here serve as models for unfolded proteins, while as Qvist and Halle say, “for folded proteins, the intricate surface topography features solvent-penetrated pockets with more substantial perturbations of water dynamics than at the convex parts of the surface.”

Poul Petersen and Rick Saykally have a new contrubution to the ongoing debate over whether the air-water surface is basic or acidic (Chem. Phys. Lett. 458, 255-261; 2008 – paper here). They use resonant UV second-harmonic generation spectroscopy to study the question, and find that the results are best understood as indicating a surface depletion of hydroxide and enhancement of hydrated protons. This paper gives a nice overview of the history of this issue and the current state of play, and offers a suggestion for why the results seem to conflict with the conclusions based on macroscopic measurements of zeta potentials at bubble surfaces.

More on gating of protein channels. Carmen Domene at Oxford and coworkers report a simulation study of potassium channels in which they look at how conformational changes in the constriction responsible for ion selectivity can also induce gating by in effect snipping the hydrogen-bonded chain of water molecules (C. Domene et al. JACS doi:10.1021/ja801792g; paper here). Dirk Gillespie at Rush University Medical Center had a recent paper on the mechanism of divalent selectivity in calcium channels (Biophys. J. 94, 1169-1184; 2008 – paper here). And he and his coworkers have a new paper using synthetic nanopores to investigate a theory for the mechanism of the anomalous mole fraction effect in ion channels, whereby two types of ion produce a lower conductance than the same concentration of either ion on its own (D. Gillespie et al., Biophys. J. 95, 609-619; 2008 – paper here). They show that single-file motion of the ions through the channel is not necessary to produce this effect.

At the recent meeting of the DFG Forschergruppe 436 in Dortmund I had the pleasure of meeting Rajesh Mishra and Roland Winter, who now have an interesting paper on the issue of amyloid polymorphisms of proteins, specifically on how cold denaturation and high pressure can dissolve protein aggregates (Angew. Chem. Int. Ed. doi:10.1002/anie.200802027 – paper here). I’ve not been able to read the full paper yet, but from talking to Rajesh I can see that this is a potentially very fruitful direction.

Also forthcoming in Angewandte Chemie, though I’ve not seen it online yet, is a paper by Martin Gruebele, Martina Havenith and colleagues entitled “Real-time detection of protein-water dynamics upon folding by terahertz absorption”, which does what it says on the can (the protein here is ubiquitin). The results provide more evidence of slaving of (some) protein dynamics to solvent motions – in this case, if I understand correctly, the coupling comes from the way hydrogen bonds between the unfolded protein backbone and water are broken and then remade as intramolecular H-bonds in the secondary structure.

In a somewhat related vein, Biman Bagchi and colleagues at the Indian Institute of Science in Bangalore have studied hydrogen-bond breaking in the hydration shell of lysozyme (B. Jana et al., J. Phys. Chem. B doi:10.1021/jp800998w – paper here). They see three different mechanisms for bond-breaking. In 80 percent of cases, the new acceptor water molecule comes from within the first coordination shell, and the old acceptor water molecule remains in the shell. Neither the incoming nor the outgoing acceptor molecules show diffusive motion. In 10 percent of cases, the new acceptor comes from the second coordination shell, with the donor being in the first. In the remaining 10 percent of cases, both of the acceptor molecules are initially in the first coordination shell, but the old acceptor moves out after bond breaking. In all cases, the donor molecule undergoes a large-angle reorientational jump on making the new bond.

Alfonso De Simone in Naples (currently at Cambridge) has sent me a couple of nice reprints. In a paper in Proteins (G. Colombo et al., Proteins 70, 863-872; 2008) he and his colleagues have looked at whether amyloid-like fibrils, here of ribonuclease A, retain native-like domains. Using MD simulations, they find that this is indeed the case in these fibrils: there are segments that retain monomer-like conformations, dynamics and hydration structures, explaining why the fibrils seem to retain some catalytic activity. They also discuss how hydration changes in polyglutamine stretches might promote hydrophobic collapse leading to aggregation (despite the fact that glutamine is generally considered to be hydrophilic). Alfonso says “a better inspection showed that the huge accessibility of glutamines to sidechain-sidechain H-bonds generated a chaotic and complex network. As a result of continuous forming and breaking of sidechain-sidechain H-bonds, the water was not able to interact stably with glutamines and presented very short residence times… Therefore the message is that dewetting can be triggered even by surfaces that are able to engage in a large number of H-bonds with water. Sometimes the dynamics of the interaction are even more important than the interaction itself.”

The other paper looks at the “Role of hydration in collagen triple helix stabilization” (A. De Simone et al., Biochem. Biophys. Res. Commun. 372, 121-125; 2008). They find, again vai MD simulations, a wide range of water residence times in the hydration layer, strongly influenced by the local peptide sequence. Moreover, the stabilizing effect of Arg and Hyp (hydroxyproline) residues on the triple helix is water-mediated.

Well, that does not clear my pile but it makes a dent. More as soon as I’m able.