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.
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3 comments:
So does that mean that the dynamics of water and the protein are always coupled? Or does the protein have some "independent" dynamics of its own at the 'critical' temp (220 K in this case) too?
A little off the topic (or perhaps not...): what is the most stable ring structure for water molecules in bulk water? Because in Richard Friesner's PNAS paper (Jan 16, 2007, p. 808), Friesner says that "five membered rings are only fleetingly observed in bulk water". But on p. 166 of your excellent book 'H20: A biography of water', you say that the most common ring structure in liquid water contains five molecules. So what's the exact stable ring structure made from these five molecules?
ashutosh,
In answer to your second question, I'm frankly puzzled. Friesner et al. cite Rahman and Stillinger (1973) in support of the idea that five-membered rings are uncommon in liquid water (because of unfavourable entropy). I used Rahman and Stillinger as the basis for suggesting in my book that 5-rings are rather common. That is what their (admittedly rather old) simulations seemed to show. I don't see where in the paper there is any claim to the effect indicated by Friesner et al.
Moreover, the notion that 5-rings are common in hydration shells is also widespread: there's a suggestion that hydrophobic groups are hydrated in a manner similar to clathrates. I'm not sure if that is actually well-established. But I don't know that there's any reason to doubt that 5-rings could form. To take an example that springs easily to hand, Loren Williams et al. have indicated that there are plenty of 5-rings hydrating DNA (Biochemistry 33, 3649; 1994 - though that paper was pointing out that 5-rings are not especially favoured). So I don't really understand why Friesner et al. make a big deal of the 5-rings they see. Perhaps I'm missing something.
As to your first point - I think the idea is that the coupling is especially strong around 220 K (I think it's clear that proteins have independent dynamics at room temp, say). Quite how tightly the coupling is supposed to be at 220 K I'm not sure - I suspect we don't quite know this yet.
Thanks for the clarification!
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