How thick-skinned is hydration?

How much water do you need to fully solvate a protein? There are many studies of protein behaviour at low water coverage, going back to the suggestion by Rupley and Careri (Adv. Protein Chem. 41, 37-172; 1991) that proteins seem to require about 0.4 g of water per gram of protein to achieve their normal functionality. Roland Winter and coworkers have investigated the notion of a percolation transition in water coverage that brings the protein dynamics to life (Oleinikova et al., J. Phys. Chem. B 109, 1988-1998; 2005; Smolin et al., J Phys. Chem. B 109, 10995-11005; 2005). Mehdi Bagheri Hamaneh and Matthias Buck at Case Western have looked at the question in a rather different light: how much water do you need to put around a protein in order to be able to simulate it realistically? They find (Biophys. J. 92, L49; 2007) that you don't need to fill up your simulation box with explicit water � a shell just two or three layers thick (using the CHARMM22/CAMP potential function) will do the job well enough. That's computationally cheap, and I suppose implies that there's not really much excuse for failing to model hydration explicitly. It also implies that the celebrated cooperativity of water dynamics in the hydration shell does not appear to extend very far � at least, perhaps one should say, for the case of lysozyme considered here.

More on the 'glass transition' at around 220 K, seemingly shown now (Chen et al., PNAS 103, 901; 2006) to be a fragile-to-strong crossover. This applies also to DNA (Chen et al., J. Chem. Phys. 125, 171103; 2006), and now Sow-Hsin Chen at MIT and coworkers have found similar behaviour for RNA, again at 220 K (http://xxx.arxiv.org/abs/physics/0703166). So this seems to be pretty universal behaviour for biomacromolecules, reinforcing the idea that the change in dynamics is imposed by the hydration water.

Masahiro Kinoshita has sent me a couple of his papers from Chem. Phys. Lett. (see them here and here) which explore his idea that "the major driving force in protein folding is a gain in water entropy". In a nutshell, they say that "a protein is designed to fold into the structure that maximizes the entropy of water under the requirement that sufficiently many intramolecular hydrogen bonds be formed to compensate the dehydration penalty." In other words, as I understand it, the enthalpies balance and what's left (governing stability) is the water entropy change. That's intriguing; I'm still struggling to see how this ties up with Jack Dunitz's suggestion (Science 264, 670; 1994; Chem. Biol. 2, 709-712; 1995) that transferring a water molecule from an ordered binding site where it is bound by an �average� hydrogen bond to the bulk involves an overall free-energy change that is close to zero, and with ideas about the importance of interactions at specific residues � the 'hotspots' discussed in the last post, and Ariel Fernandez's notion of dehydrons, for instance. One day, perhaps, it will all make sense to me.