My new resolution is to try to post more often and in smaller chunks, not least to avoid an impression of this site being moribund. With that in mind, I acknowledge that there is a fair bit of old stuff to catch up on which is not yet covered here. I also hope, when I have a moment, to find a way of posting that will make this blog accessible in China, which it is not at present because it seems the whole hosting network is blocked due to Google-related wrangles.
Water in protein hydration shells has retarded dynamics, for example in terms of reorientation. But how much and why? Reports vary, from slowing by a factor of a few to several orders of magnitude. Damien Laage and colleagues at ENS in Paris have tried to clarify the situation with simulations of lysozyme (F. Sterpone et al., JACS 134, 4116; 2012 � paper here). They find that most (80%) of the hydration water is slowed by a factor of just 2-3, and that the dynamics seem to be dominated by the same kind of activated jumps between H-bond acceptors as in the bulk. This slowdown seems to be due to an excluded-volume effect from the proximity of the protein surface, which reduces the number of transition-state configurations for reorienting jumps. The remaining water may be slowed to a greater degree, apparently due to water bound within clefts and pockets on the protein surface, where generally it is bound to H-bond acceptors.
Ben Corry and Michael Thomas at the University of Western Australia say that water plays a role in the selectivity of voltage-gated sodium channels (JACS 134, 1840; 2012 � paper here). Simulations based on a recent crystal structure show that unlike sodium, potassium ions can�t fit between a plane of glutamate residues with water molecules bridging the ion and the carboxylate groups � so these latter ions are excluded even though in principle they could pass through the pore with their complete hydration shell. This suggests that there are more subtle structural factors at work than (as has been suggested previously) simply the free-energy penalty of ion dehydration.
The hydrophobic effect and its role in the assembly of hydrophobic particles has generally been considered from the perspective of an equilibrium process, with no account of hydrodynamic factors. Bruce Berne and his coworkers at Columbia now seek to rectify this (J. A. Morrone et al., J. Phys. Chem. B 116, 378; 2012 � paper here). They simulate the interactions of two fullerenes in water, taking into account how molecular-scale hydrodynamics affects solvent density fluctuations and drying transitions. Perhaps unsurprisingly, a continuum picture breaks down at the smallest length scales : for example, the friction coefficient deviates from the continuum prediction at small particle separations, and can become non-monotonic due to layering. In general, these hydrodynamic effects can significantly reduce the diffusion-controlled rate constant for hydrophobic assembly. As the authors say, how such effects would become manifest in the crowded environment of the cell is another matter.
When is a protein unfolded? It�s not such an easy question as one might suppose: Sunilkumar Puthenpurackal Narayanan and colleagues in Japan say (Biophys. J. 102, L08 � paper here) that Catherine Royer and colleagues have recently found that staphylococcal nuclease can show a proton NMR signal at high pressures indicative of complete folding while Trp fluorescence data suggest significant unfolding. Narayanan et al. see something comparable for a subdomain of the transcription factor c-Myb R2 at high pressure and low temperature. This, they say, seems to be explicable on the basis that the protein remains folded but extensively hydrated, owing to water filling of a large internal cavity. This adds to the ongoing debate about the mechanism of pressure-induced denaturation, which some say is caused by the intrusion of water. More on this in a later post.
I wish I had a better grasp of a paper by Vladimir Sirotkin and Aigul Khadiullina of the Kazan Federal University in Russia on excess partial enthalpies of water and proteins (J. Chem. Phys. B 115, 15110; 2011 � paper here). But the key point seems to be that the progression from more or less dehydrated to fully hydrated states of several different proteins follow the same trajectory, at least in thermodynamic terms. The excess partial enthalpy is initially dominated by water, but then up to a weight fraction of 0.06 both protein and water contribute significantly. At this point the charged groups on the protein are hydrated and the proteins become flexible. And by a weight fraction of 0.5, hydration is complete and further changes are due only to contributions from the proteins. This seems loosely to be in accord with notions of a roughly universal �critical coverage� for a protein hydration shell.
Water in protein hydration shells has retarded dynamics, for example in terms of reorientation. But how much and why? Reports vary, from slowing by a factor of a few to several orders of magnitude. Damien Laage and colleagues at ENS in Paris have tried to clarify the situation with simulations of lysozyme (F. Sterpone et al., JACS 134, 4116; 2012 � paper here). They find that most (80%) of the hydration water is slowed by a factor of just 2-3, and that the dynamics seem to be dominated by the same kind of activated jumps between H-bond acceptors as in the bulk. This slowdown seems to be due to an excluded-volume effect from the proximity of the protein surface, which reduces the number of transition-state configurations for reorienting jumps. The remaining water may be slowed to a greater degree, apparently due to water bound within clefts and pockets on the protein surface, where generally it is bound to H-bond acceptors.
Ben Corry and Michael Thomas at the University of Western Australia say that water plays a role in the selectivity of voltage-gated sodium channels (JACS 134, 1840; 2012 � paper here). Simulations based on a recent crystal structure show that unlike sodium, potassium ions can�t fit between a plane of glutamate residues with water molecules bridging the ion and the carboxylate groups � so these latter ions are excluded even though in principle they could pass through the pore with their complete hydration shell. This suggests that there are more subtle structural factors at work than (as has been suggested previously) simply the free-energy penalty of ion dehydration.
The hydrophobic effect and its role in the assembly of hydrophobic particles has generally been considered from the perspective of an equilibrium process, with no account of hydrodynamic factors. Bruce Berne and his coworkers at Columbia now seek to rectify this (J. A. Morrone et al., J. Phys. Chem. B 116, 378; 2012 � paper here). They simulate the interactions of two fullerenes in water, taking into account how molecular-scale hydrodynamics affects solvent density fluctuations and drying transitions. Perhaps unsurprisingly, a continuum picture breaks down at the smallest length scales : for example, the friction coefficient deviates from the continuum prediction at small particle separations, and can become non-monotonic due to layering. In general, these hydrodynamic effects can significantly reduce the diffusion-controlled rate constant for hydrophobic assembly. As the authors say, how such effects would become manifest in the crowded environment of the cell is another matter.
When is a protein unfolded? It�s not such an easy question as one might suppose: Sunilkumar Puthenpurackal Narayanan and colleagues in Japan say (Biophys. J. 102, L08 � paper here) that Catherine Royer and colleagues have recently found that staphylococcal nuclease can show a proton NMR signal at high pressures indicative of complete folding while Trp fluorescence data suggest significant unfolding. Narayanan et al. see something comparable for a subdomain of the transcription factor c-Myb R2 at high pressure and low temperature. This, they say, seems to be explicable on the basis that the protein remains folded but extensively hydrated, owing to water filling of a large internal cavity. This adds to the ongoing debate about the mechanism of pressure-induced denaturation, which some say is caused by the intrusion of water. More on this in a later post.
I wish I had a better grasp of a paper by Vladimir Sirotkin and Aigul Khadiullina of the Kazan Federal University in Russia on excess partial enthalpies of water and proteins (J. Chem. Phys. B 115, 15110; 2011 � paper here). But the key point seems to be that the progression from more or less dehydrated to fully hydrated states of several different proteins follow the same trajectory, at least in thermodynamic terms. The excess partial enthalpy is initially dominated by water, but then up to a weight fraction of 0.06 both protein and water contribute significantly. At this point the charged groups on the protein are hydrated and the proteins become flexible. And by a weight fraction of 0.5, hydration is complete and further changes are due only to contributions from the proteins. This seems loosely to be in accord with notions of a roughly universal �critical coverage� for a protein hydration shell.
Hello, my name is Jack Sparrow. I'm a 50 year old self-employed Pirate from the Caribbean.
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