More of the same

Two papers provide additional evidence of perturbations to water’s structure and properties at interfaces. The long saga about density depletion at hydrophobic surfaces now seems to be settling down in favour of the position that there is indeed a degree of depletion when the surfaces are strongly hydrophobic, but only over angstrom distances. That is supported by the Monte Carlo simulations of Jiri Janacek and Roland Netz (Langmuir 23, 8417; 2007), who see depletion layers 1.5-2 Å thick at ordered hydrocarbon surfaces with contact angles of 110-130 degrees.

And the idea that water confined at the nanoscale between surfaces has greatly enhanced viscosity (see, for example, Li et al., Phys. Rev. B 75, 115415; 2007) is supported in further experiments by Tai-De Li and Elisa Riedo at Georgia Tech, who have investigated water’s nonlinear viscoelastic behaviour using the AFM (www.arxiv.org/abs/ 0707.2521).

A proton switch in GFP

Emission from green fluorescent protein (GFP) is one of the most widely used methods of molecular marking in cell biology, since GFP can be prepared as a fusion protein with just about any other gene product. But the fluorescence behaviour is curious and hasn’t been fully explained. In particular, it shows a t**-3/2 time dependence in the long-time tail at room temperature, but switches to a t**-1/2 dependence below 230 K. Fluorescence involves a photoexcited proton transfer from the chromophore, which is thought to occur along a hydrogen-bonded chain involving various residues and bound water molecules. Noam Agmon has modelled this process, considering the ‘proton wire’ to be rather longer than is normally thought and to have within it a switch at a threonine residue (Thr203) with a large activation energy for proton migration (J. Phys. Chem. B 111, 7870; 2007). The rapid migration of the proton is held up at this switch point for typically 300 ps at room temperature. This model can explain both the t**-3/2 behaviour at room temperature and the changeover to different asymptotics at 230 K. Here’s another example of water and hydrogen-bonding residues collaborating to engineer biological function.

Proteins that dry in a flash

Do proteins aggregate and fold in an abrupt ‘dewetting’ transition that expels water from between hydrophobic surfaces, or is the water squeezed out more gradually? The former idea has been popularised by Lum, Weeks and Chandler (J. Phys. Chem. B 103, 4570; 1999), who argued that this drying transition should be expected for surfaces of around 1 nm or more in at least one dimension. But observations and simulations of protein aggregation and folding haven’t generally supported it (see, for example, Zhou et al, Science 305, 1605; 2004). Yet Bruce Berne and his colleagues (who conducted that study in Science) have found that the tetrameric channel-forming protein melittin does seem to show a dewetting transition (Liu et al., Nature 437, 159; 2005). Is that a rarity, even a unique case, or might other proteins also exhibit dewetting? Berne and co. have performed a survey of the protein data bank to search for other structures that might show similar behaviour (Hua et al., J. Phys. Chem. B, 10.1021/jp0704923). The message is that dewetting is rare, but does happen in a few other cases too: the authors find several other examples of multi-domain proteins that display it in the final stages of folding. Specifically, they identify two two-domain proteins six dimers and three tetramers that behave this way. It seems that any significant number of polar residues in the hydrophobic core (which is common) is generally enough to suppress dewetting. Using the same tools, however, Berne and colleagues find preliminary evidence that dewetting may also sometimes play a role in ligand binding.

What proteins do to water

Why does protein hydration water display anomalous dynamics? There is a huge literature on this, particularly in terms of quantifying the effect. Clearly the effect is heterogeneous and complex, but there is some reason to suppose that in general hydration water exhibits anomalous diffusion, the translational motion following a t**0.6 time dependence rather than Brownian t**0.5.

Francesco Pizzitutti at Saclay, Peter Rossky at Texas at Austin, and their coworkers have tried to figure out what is going on using MD simulations (J. Phys. Chem. B 111, 7584; 2007). They consider two aspects of the problem: the effect of protein topology and of static, energetic effects due to, e.g. pinning (polar water-binding) sites, and dynamic effects due to protein motion. Both of these slow down translation, but rotational retardation seems to come only from energetic (electrostatic) effects: when these are switched off, the water molecules actually reorient faster than in bulk. Translational motion happens by water molecules jumping between sites previously occupied by other waters, but also to sites previously occupied by protein groups – hence the involvement of protein motions. Without this protein motion, the options for water hopping are smaller, and so the diffusional retardation is even greater.

What about collective effects due to the hydrogen-boded network? These do seem to exist, and indeed to be strong – the effect of electrostatic pinning sites can percolate throughout the entire surface layer. That fits with the notion of percolation-dependent hydration dynamics discussed by Oleinikova et al. (Phys. Rev. Lett. 95, 247802; 2005).

This is a very nice paper that helps to prise apart the many factors operating simultaneously.