Tuesday, May 1, 2007

More Hofmeister head-scratching

A paper by Dér et al. [J. Phys. Chem. B, doi:10.1021/jp066206p] makes the bold claim of providing a general microscopic interpretation of Hofmeister effects – the ion-specific salting-in or salting-out of proteins. I’m not sure that it succeeds. The basic idea is that the ions induce changes to the protein-water interfacial tension: so-called kosmotropes make the interface more hydrophobic, and chaotropes make it more hydrophilic. I can’t help feeling that the paper is hampered from the outset by an insistence on retaining the chaotrope/kosmotrope terminology, which was coined to suggest that the respective ions ‘break’ or ‘make’ ‘water structure’. There’s no evidence that ions do either, at least in terms of exerting any global influence on the hydrogen-bonded network. Indeed, Dér et al. acknowledge that spectroscopic studies [Omta et al., Science 301, 347; 2003] show no change in hydrogen-bonding on addition of ions beyond their first hydration shell. As far as I can make out, they seem to say that preferential segregation of ions at or away from the interface means that localized effects on H-bonding can be specifically felt there. But it’s not clear to me what they are thinking of in alluding to this surface segregation of ions – there’s no reference, for example, to the studies of that (at the air-water interface) by Jungwirth, Saykally and others. Nor do the authors seem to take into account how this picture applies to hydrophobic surfaces (Bruce Berne has studied this, and found ion-specific segregation). In any event, what results seems rather unsatisfactory, since we are then left with the confusing chao/kosmotrope terminology but a hint that in fact all the action is taking place at the interface (which is probably the case) – and an attempt to explain that action in terms of macroscopic interfacial tensions (which are not known anyway for protein-water interfaces). I can’t help thinking that it remains more useful to think more explicitly about how ions might modify the nature of the microscopic protein-water interface, and how this picture changes when two surfaces come together (so that, say, adsorbed ions are excluded).

Greg Voth’s group has just published a very nice review on proton transport in aqueous systems, including all the work on ‘water wires’ in aquaporin, M2, cytochromes and other proteins [J. Phys. Chem. B 111, 4300-4314; 2007].

Sylvia McLain and colleagues have conducted an extensive neutron-scattering study of the structure of proline solutions [J. Phys. Chem. B 111, 45568-4580; 2007]. Proline acts as an osmolyte or osmoprotectant, apparently protecting proteins against denaturation under water stress. It has been suggested that this is somehow due to proline clustering in solution, but McLain et al. find no strong evidence of that. Indeed, proline seems barely to perturb water’s hydrogen-bonded network at all, while remaining sufficiently hydrated to attain good solubility. They speculate that, despite the only weak tendency of prolines to cluster, they might form a protective sheath around proteins, chaperoning them to prevent denaturation.
Update: McLain and colleagues have just published a comparison of these experimental results with computer simulations (which show reasonable agreement): J. Phys. Chem. B 111, 8210; 2007.

No comments: