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.