Garegin Papoian has extended his previous studies of how water-mediated contacts influence protein folding, with a new paper with Christopher Materese and Christa Goldmon (C. K. Materese et al., PNAS doi:10.1073/pnas.0801850105 – paper here). The basic notion is that a variety of contacts in the folding peptide – hydrophobic, hydrophilic, salt bridges – are ‘tried out’ during the folding process and filtered down to a subset of preferred interactions in a hierarchical branching process. This paper shows that many of these contacts are mediated by bridging water molecules, and that subsets of such interactions are characteristic of certain basins in the folding landscape. It adds to the argument that explicit water is essential for a full picture of the folding process.
Valerie Daggett and colleagues at the University of Washington in Seattle have carried out simulations of aquaporin embedded in a lipid bilayer to study the role of protein fluctuations on water transport (N. Smolin et al., Biophys. J. 95, 1089-1098; 2008 – paper here). Their aim was to look at some of the apparent discrepancies in earlier studies of how water passes through the protein pore in a hydrogen-bonded wire (e.g. Tajkhorshid et al., Science 296, 525-530; 2002; de Greet & Grubmuller, Science 294, 2353-2357; 2001). The key action seems to happen in the narrow constriction at the centre of the channel called the NPA region. Here, the dynamics of two asparagine residues seem to play a crucial role in aligning the water molecules for transport to occur. But beyond the constriction is a ‘valve’ region in which two residues, His76 and Val155, act to control the flow by potentially swinging into the channel to block the passage of the water molecules. The emerging picture, then, is of a remarkably orchestrated collaboration of side-chain and water dynamics to regulate the progress of the water along the ‘wire’.
H. Nagase of Hoshi University in Tokyo and his coworkers have continued their exploration of the molecular mechanisms of anhydrobiosis and how trehalose acts as a bioprotectant in this regard (H. Nagase et al., J. Phys. Chem. B. 112, 9105-9111; 2008 – paper here). They have studied the crystal structure of trehalose anhydrate, and find that it contains a one-dimensional channel threading between the trehalose molecules which may be filled with water in the dihydrate form of solid trehalose. This water uptake facilitates the transformation from the anhydrate to the dihydrate, and effectively makes the crystalline form a potential source and sink of water. If I understand this rightly, I believe the idea is then that this ‘water sponge’ prevents uptake of water by the amorphous (glassy) phase of trehalose thought to be responsible for bioprotection, which would otherwise lower its glass transition temperature.
Fernando Bresme at Imperial College and his coworkers have returned to the controversial question of a ‘hydrophobic gap’ or depletion layer at the interface of water with a hydrophobic surface (Phys. Rev. Lett. 101, 056102; 2008 – paper here). They model this interface as that between water and dodecane or hexane, which they study using computer simulations. Their objective is to decouple the intrinsic width and density profile of the interface with the effect of fluctuations from capillary waves, which will blur the details. They find that at 300 K water at the interface resembles that at the air-water interface – despite the fact that there is no appreciable intervening vapour film because the system is far from the drying transition. And the interface is rather rigid: corrugations remain well below a molecular diameter. But the water structure is significantly perturbed, with layering similar to that seen at a hard surface. Of course, this leaves open the question of what a nanoscopic film of water looks like between two such surfaces (see below), let alone the issue of how (if at all) a more rigid hydrophobic surface changes the situation. But it does seem to support the growing consensus that any ‘hydrophobic gap’ is extremely narrow.
On the same issue, there’s an interesting exchange in Phys. Rev. Lett. between Ben Ocko and colleagues and Steve Granick and coworkers (B. Ocko et al., Phys. Rev. Lett. 101, 039601 and A. Poynor et al., 039602; 2008 – letters here and here). Poynor et al. claimed previously (Phys. Rev. Lett. 97, 266101; 2006) that they see a depletion layer 2-4 Å thick with a reduced water density of at least 40 percent of the bulk. Ocko et al. say that, if the hydrogen-rich methyl groups of the hydrophobic monolayer are taken into account, the density deficit is much reduced, and might in fact be explained instead by local water orientation. Poynor et al. reject the latter interpretation, but agree that, as they stated, their originals density depletion was cited only as an upper bound. They point out that there does now seem to be agreement that a depletion zone exists (and, I guess, that it is very narrow and certainly not gas-like), and argue that the focus now should be on the role of fluctuations in the interfacial density. David Chandler has argued that indeed it’s the fluctuations (as opposed to the average equilibrium state) that matter for any discussion of how dewetting might occur between two such surfaces.
I have been meaning for some time to mention a paper by Alexander Pertsin and Michael Grunze (Langmuir 24, 4750-4755; 2008 – paper here) on simulations of the shear behaviour of water films between hydrophilic surfaces. Perhaps the delay was fortuitous, because into this discussion there now comes an experimental paper by K. B Jinesh and Joost Frenken at Leiden (Phys. Rev. Lett. 101, 036101; 2008 – paper here). Pertsin and Grunze previously simulated water monolayers (Langmuir 24, 135; 2008 – paper here), and found that they could observe essentially solid-like configurations in the confined layer. They now say that solidification can happen for bilayers too when sheared quasi-statically (that is, with an infinitely small shear rate) – but only for a small range of wall-to-wall separation, where the separation between the two monolayers is favourable for the formation of hydrogen bonds between them. The solid-like shear behaviour also depends on the relative alignment and period of the wall lattices. And importantly, the solid-like shear behaviour does not involve film crystallization. For trilayers, there is no solid-like behaviour at all.
So then, a complex picture. Now, already this seems to complicate the picture reported by Zhu and Granick (Phys. Rev. Lett. 87, 096104; 2001), where oscillatory shear of electrolyte films between mica showed no solid-like signature. One might add that Jacob Klein and colleagues have also seen the retention of fluidity in sub-nanometre confined water films under shear (U. Raviv et al., Nature 413, 51-54; 2001). Yet Jinesh and Frenken claim to see a solid-like response in their friction-force measurements of water between a graphite surface and a tungsten tip. Specifically, they see stick-slip behaviour which seems to change, with increasing humidity, from that expected for graphite corrugation to that with a different periodicity (around 0.4 nm), similar to a lattice periodicity of ice. The film thickness here is not known for sure, but is less than about 2 nm. (I notice that they have made this claim before on the basis of different evidence, which has caused a little confusion.)
Now, I’ve seen some criticisms of this latest work – for example, that it seems to attribute thermodynamic transitions from dynamic mechanical measurements, that it ignores the possibility of surface reconstructions of bulk ice or of a tip-sample potential and the role of the lateral spring constant in the cantilever in determining the 0.4 nm periodicity. This is a tricky issue – it would be unfair to level unattributed criticisms at the work, but neither can I pretend I haven’t heard them. I guess I can only say that there seems to be a debate in store, and until that happens we might best regard the results as no more than suggestive. In any event, if Pertsin and Grunze are right, there is likely to be a great deal of further subtlety to the question, not least in terms of the lattice periodicities and the hydrophobicity/hydrophilicity of the surfaces.
Staying with fundamentals, Noam Agmon, Greg Voth and their colleagues present a new look at the details of proton transport in water – classically explained by the Grotthuss hopping mechanism but now known to be a more complex, cooperative process (O. Markovitch et al., J. Phys. Chem. B 112, 9456-9466; 2008 – paper here). Their quantum-chemical calculations offer a fine-grained picture involving a range of time and distance scales: a ‘dance’ that embraces proton motions and water reorientations in both the first and the second hydration shells of the central hydronium ion.
An interesting paper by Haoran Li and colleagues at Zhejiang University in Hangzhou (X. Hu et al., J. Phys. Chem. B doi:10.1021/jp8028903 – paper here) explores not a biologically relevant process per se – the iron-porphyrin-catalysed activation of methane and methanol – but one that has interesting parallels to the functions of some cytochromes and horseradish peroxidise. In both of those latter cases, water molecules have been found to play important roles, particularly by providing bridges for proton transport to or from the heme group. Water has also been found to assist metal-porphyrin-catalysed oxidation in trace amounts, but to suppress the reaction when present in greater amounts. Li et al. find that a water molecule near the iron porphyrin can either assist or inhibit the catalytic processes considered here, depending on where it sits.
Wednesday, August 6, 2008
Wednesday, July 23, 2008
Hydration dynamics, amyloids, and more
My pile of water-related papers is stacking up worryingly, so let me now try to clear it. Thanks again to everyone who has sent me papers – it is always a pleasure to receive them.
Roberto Senesi and Antonino Pietropaolo at Rome and their colleagues have been producing a succession of papers in which they use inelastic neutron scattering to study the momentum distributions of protons in water in a variety of settings: in nano-confined systems (G. Reiter et al., Phys. Rev. Lett. 97, 247801; 2006 – paper here; and V. Garbuio et al., J. Chem. Phys. 127, 154501; 2007 – paper here), in supercooled water (A. Pietropaolo et al., Phys. Rev. Lett. 100, 127802; 2008 – paper here) and the ambient liquid and supercritical phase (C. Pantalei et al., Phys. Rev. Lett. 100, 177801; 2008 – paper here), and in a protein hydration shell (R. Senesi & A. Pietropaolo, Phys. Rev. Lett. 98, 138102; 2007 – paper here). The last of these is of course particularly relevant here. The authors study the momentum distributions for hydration protons around lysozyme both above (290 K) and below (180 K) the dynamical transition at around 220 K. At 290 K, the results are consistent with a hydration shell that is slightly denser than bulk water, with a smaller oxygen-oxygen distance that confines the protons in a double well, with the possibility of tunnelling between minima. This suggests that tunnelling may occur even at room temperature ion the hydration shell, with potential implications for biological function. That, of course, is something that would be picked up in simulations only in a full quantum-chemical treatment.
There’s an important paper by Johan Qvist and Bertil Halle in JACS (doi:10.1021/ja802668w paper here) on rotational dynamics of water in hydrophobic hydration shells, probed by deuterium NMR. They find for four partly hydrophobic solutes, including two peptides and two osmolytes, that below 255 K hydration water rotates with a lower activation energy, and faster if the temperature is low enough, than it does in the bulk. As they say, “these findings reverse the classical ‘iceberg’ view of hydrophobic hydration by indicating that hydrophobic hydration water is less ice-like than bulk water.” It will be good to put that idea finally to rest. Moreover, the two osmolytes have opposite effects on protein stability but the same effect on water dynamics, again challenging the common view that somehow ‘water structure’ is responsible for these effects. As the authors say, “Such poetic explanations may be misleading unless they are accompanied by a precise definition of water structure. Indeed, much of the confusion in the literature stems from indiscriminate use of the word ‘structure’. Furthermore, the connection between water dynamics and structure is non-trivial.” These NMR results do, however, seem to conflict with quasi-elastic neutron scattering studies (e.g. D. Russo et al., Biophys. J. 86, 1852; 2004), and Qvist and Halle suggest some reasons for that. A final word of caution: the small peptides here serve as models for unfolded proteins, while as Qvist and Halle say, “for folded proteins, the intricate surface topography features solvent-penetrated pockets with more substantial perturbations of water dynamics than at the convex parts of the surface.”
Poul Petersen and Rick Saykally have a new contrubution to the ongoing debate over whether the air-water surface is basic or acidic (Chem. Phys. Lett. 458, 255-261; 2008 – paper here). They use resonant UV second-harmonic generation spectroscopy to study the question, and find that the results are best understood as indicating a surface depletion of hydroxide and enhancement of hydrated protons. This paper gives a nice overview of the history of this issue and the current state of play, and offers a suggestion for why the results seem to conflict with the conclusions based on macroscopic measurements of zeta potentials at bubble surfaces.
More on gating of protein channels. Carmen Domene at Oxford and coworkers report a simulation study of potassium channels in which they look at how conformational changes in the constriction responsible for ion selectivity can also induce gating by in effect snipping the hydrogen-bonded chain of water molecules (C. Domene et al. JACS doi:10.1021/ja801792g; paper here). Dirk Gillespie at Rush University Medical Center had a recent paper on the mechanism of divalent selectivity in calcium channels (Biophys. J. 94, 1169-1184; 2008 – paper here). And he and his coworkers have a new paper using synthetic nanopores to investigate a theory for the mechanism of the anomalous mole fraction effect in ion channels, whereby two types of ion produce a lower conductance than the same concentration of either ion on its own (D. Gillespie et al., Biophys. J. 95, 609-619; 2008 – paper here). They show that single-file motion of the ions through the channel is not necessary to produce this effect.
At the recent meeting of the DFG Forschergruppe 436 in Dortmund I had the pleasure of meeting Rajesh Mishra and Roland Winter, who now have an interesting paper on the issue of amyloid polymorphisms of proteins, specifically on how cold denaturation and high pressure can dissolve protein aggregates (Angew. Chem. Int. Ed. doi:10.1002/anie.200802027 – paper here). I’ve not been able to read the full paper yet, but from talking to Rajesh I can see that this is a potentially very fruitful direction.
Also forthcoming in Angewandte Chemie, though I’ve not seen it online yet, is a paper by Martin Gruebele, Martina Havenith and colleagues entitled “Real-time detection of protein-water dynamics upon folding by terahertz absorption”, which does what it says on the can (the protein here is ubiquitin). The results provide more evidence of slaving of (some) protein dynamics to solvent motions – in this case, if I understand correctly, the coupling comes from the way hydrogen bonds between the unfolded protein backbone and water are broken and then remade as intramolecular H-bonds in the secondary structure.
In a somewhat related vein, Biman Bagchi and colleagues at the Indian Institute of Science in Bangalore have studied hydrogen-bond breaking in the hydration shell of lysozyme (B. Jana et al., J. Phys. Chem. B doi:10.1021/jp800998w – paper here). They see three different mechanisms for bond-breaking. In 80 percent of cases, the new acceptor water molecule comes from within the first coordination shell, and the old acceptor water molecule remains in the shell. Neither the incoming nor the outgoing acceptor molecules show diffusive motion. In 10 percent of cases, the new acceptor comes from the second coordination shell, with the donor being in the first. In the remaining 10 percent of cases, both of the acceptor molecules are initially in the first coordination shell, but the old acceptor moves out after bond breaking. In all cases, the donor molecule undergoes a large-angle reorientational jump on making the new bond.
Alfonso De Simone in Naples (currently at Cambridge) has sent me a couple of nice reprints. In a paper in Proteins (G. Colombo et al., Proteins 70, 863-872; 2008) he and his colleagues have looked at whether amyloid-like fibrils, here of ribonuclease A, retain native-like domains. Using MD simulations, they find that this is indeed the case in these fibrils: there are segments that retain monomer-like conformations, dynamics and hydration structures, explaining why the fibrils seem to retain some catalytic activity. They also discuss how hydration changes in polyglutamine stretches might promote hydrophobic collapse leading to aggregation (despite the fact that glutamine is generally considered to be hydrophilic). Alfonso says “a better inspection showed that the huge accessibility of glutamines to sidechain-sidechain H-bonds generated a chaotic and complex network. As a result of continuous forming and breaking of sidechain-sidechain H-bonds, the water was not able to interact stably with glutamines and presented very short residence times… Therefore the message is that dewetting can be triggered even by surfaces that are able to engage in a large number of H-bonds with water. Sometimes the dynamics of the interaction are even more important than the interaction itself.”
The other paper looks at the “Role of hydration in collagen triple helix stabilization” (A. De Simone et al., Biochem. Biophys. Res. Commun. 372, 121-125; 2008). They find, again vai MD simulations, a wide range of water residence times in the hydration layer, strongly influenced by the local peptide sequence. Moreover, the stabilizing effect of Arg and Hyp (hydroxyproline) residues on the triple helix is water-mediated.
Well, that does not clear my pile but it makes a dent. More as soon as I’m able.
Roberto Senesi and Antonino Pietropaolo at Rome and their colleagues have been producing a succession of papers in which they use inelastic neutron scattering to study the momentum distributions of protons in water in a variety of settings: in nano-confined systems (G. Reiter et al., Phys. Rev. Lett. 97, 247801; 2006 – paper here; and V. Garbuio et al., J. Chem. Phys. 127, 154501; 2007 – paper here), in supercooled water (A. Pietropaolo et al., Phys. Rev. Lett. 100, 127802; 2008 – paper here) and the ambient liquid and supercritical phase (C. Pantalei et al., Phys. Rev. Lett. 100, 177801; 2008 – paper here), and in a protein hydration shell (R. Senesi & A. Pietropaolo, Phys. Rev. Lett. 98, 138102; 2007 – paper here). The last of these is of course particularly relevant here. The authors study the momentum distributions for hydration protons around lysozyme both above (290 K) and below (180 K) the dynamical transition at around 220 K. At 290 K, the results are consistent with a hydration shell that is slightly denser than bulk water, with a smaller oxygen-oxygen distance that confines the protons in a double well, with the possibility of tunnelling between minima. This suggests that tunnelling may occur even at room temperature ion the hydration shell, with potential implications for biological function. That, of course, is something that would be picked up in simulations only in a full quantum-chemical treatment.
There’s an important paper by Johan Qvist and Bertil Halle in JACS (doi:10.1021/ja802668w paper here) on rotational dynamics of water in hydrophobic hydration shells, probed by deuterium NMR. They find for four partly hydrophobic solutes, including two peptides and two osmolytes, that below 255 K hydration water rotates with a lower activation energy, and faster if the temperature is low enough, than it does in the bulk. As they say, “these findings reverse the classical ‘iceberg’ view of hydrophobic hydration by indicating that hydrophobic hydration water is less ice-like than bulk water.” It will be good to put that idea finally to rest. Moreover, the two osmolytes have opposite effects on protein stability but the same effect on water dynamics, again challenging the common view that somehow ‘water structure’ is responsible for these effects. As the authors say, “Such poetic explanations may be misleading unless they are accompanied by a precise definition of water structure. Indeed, much of the confusion in the literature stems from indiscriminate use of the word ‘structure’. Furthermore, the connection between water dynamics and structure is non-trivial.” These NMR results do, however, seem to conflict with quasi-elastic neutron scattering studies (e.g. D. Russo et al., Biophys. J. 86, 1852; 2004), and Qvist and Halle suggest some reasons for that. A final word of caution: the small peptides here serve as models for unfolded proteins, while as Qvist and Halle say, “for folded proteins, the intricate surface topography features solvent-penetrated pockets with more substantial perturbations of water dynamics than at the convex parts of the surface.”
Poul Petersen and Rick Saykally have a new contrubution to the ongoing debate over whether the air-water surface is basic or acidic (Chem. Phys. Lett. 458, 255-261; 2008 – paper here). They use resonant UV second-harmonic generation spectroscopy to study the question, and find that the results are best understood as indicating a surface depletion of hydroxide and enhancement of hydrated protons. This paper gives a nice overview of the history of this issue and the current state of play, and offers a suggestion for why the results seem to conflict with the conclusions based on macroscopic measurements of zeta potentials at bubble surfaces.
More on gating of protein channels. Carmen Domene at Oxford and coworkers report a simulation study of potassium channels in which they look at how conformational changes in the constriction responsible for ion selectivity can also induce gating by in effect snipping the hydrogen-bonded chain of water molecules (C. Domene et al. JACS doi:10.1021/ja801792g; paper here). Dirk Gillespie at Rush University Medical Center had a recent paper on the mechanism of divalent selectivity in calcium channels (Biophys. J. 94, 1169-1184; 2008 – paper here). And he and his coworkers have a new paper using synthetic nanopores to investigate a theory for the mechanism of the anomalous mole fraction effect in ion channels, whereby two types of ion produce a lower conductance than the same concentration of either ion on its own (D. Gillespie et al., Biophys. J. 95, 609-619; 2008 – paper here). They show that single-file motion of the ions through the channel is not necessary to produce this effect.
At the recent meeting of the DFG Forschergruppe 436 in Dortmund I had the pleasure of meeting Rajesh Mishra and Roland Winter, who now have an interesting paper on the issue of amyloid polymorphisms of proteins, specifically on how cold denaturation and high pressure can dissolve protein aggregates (Angew. Chem. Int. Ed. doi:10.1002/anie.200802027 – paper here). I’ve not been able to read the full paper yet, but from talking to Rajesh I can see that this is a potentially very fruitful direction.
Also forthcoming in Angewandte Chemie, though I’ve not seen it online yet, is a paper by Martin Gruebele, Martina Havenith and colleagues entitled “Real-time detection of protein-water dynamics upon folding by terahertz absorption”, which does what it says on the can (the protein here is ubiquitin). The results provide more evidence of slaving of (some) protein dynamics to solvent motions – in this case, if I understand correctly, the coupling comes from the way hydrogen bonds between the unfolded protein backbone and water are broken and then remade as intramolecular H-bonds in the secondary structure.
In a somewhat related vein, Biman Bagchi and colleagues at the Indian Institute of Science in Bangalore have studied hydrogen-bond breaking in the hydration shell of lysozyme (B. Jana et al., J. Phys. Chem. B doi:10.1021/jp800998w – paper here). They see three different mechanisms for bond-breaking. In 80 percent of cases, the new acceptor water molecule comes from within the first coordination shell, and the old acceptor water molecule remains in the shell. Neither the incoming nor the outgoing acceptor molecules show diffusive motion. In 10 percent of cases, the new acceptor comes from the second coordination shell, with the donor being in the first. In the remaining 10 percent of cases, both of the acceptor molecules are initially in the first coordination shell, but the old acceptor moves out after bond breaking. In all cases, the donor molecule undergoes a large-angle reorientational jump on making the new bond.
Alfonso De Simone in Naples (currently at Cambridge) has sent me a couple of nice reprints. In a paper in Proteins (G. Colombo et al., Proteins 70, 863-872; 2008) he and his colleagues have looked at whether amyloid-like fibrils, here of ribonuclease A, retain native-like domains. Using MD simulations, they find that this is indeed the case in these fibrils: there are segments that retain monomer-like conformations, dynamics and hydration structures, explaining why the fibrils seem to retain some catalytic activity. They also discuss how hydration changes in polyglutamine stretches might promote hydrophobic collapse leading to aggregation (despite the fact that glutamine is generally considered to be hydrophilic). Alfonso says “a better inspection showed that the huge accessibility of glutamines to sidechain-sidechain H-bonds generated a chaotic and complex network. As a result of continuous forming and breaking of sidechain-sidechain H-bonds, the water was not able to interact stably with glutamines and presented very short residence times… Therefore the message is that dewetting can be triggered even by surfaces that are able to engage in a large number of H-bonds with water. Sometimes the dynamics of the interaction are even more important than the interaction itself.”
The other paper looks at the “Role of hydration in collagen triple helix stabilization” (A. De Simone et al., Biochem. Biophys. Res. Commun. 372, 121-125; 2008). They find, again vai MD simulations, a wide range of water residence times in the hydration layer, strongly influenced by the local peptide sequence. Moreover, the stabilizing effect of Arg and Hyp (hydroxyproline) residues on the triple helix is water-mediated.
Well, that does not clear my pile but it makes a dent. More as soon as I’m able.
Thursday, July 3, 2008
Hangzhou Water 08
Time, I think, for this announcement of a forthcoming meeting in China. Apologies that the web link below isn't up and running yet, but I'm sure it soon will be.
Workshop on Water at Biological Interfaces
Hangzhou Water08
Oct. 27-28, 2008, Hangzhou, China
http://www.sinap.ac.cn/water08/index.html
First Announcement & Call for papers
Hangzhou Water08 is sponsored by the Shanghai Institute of Applied Physics (SINAP), cosponsored by the Zhejiang University, Organized by Shanghai Institute of Applied Physics, Chinese Academy of Sciences, and supported by National Science Foundation of China and the Chinese Academy of Science, and Ministry of Science and Technology of the People’s Republic of China
Water at biological interfaces plays a crucial role in cell and molecular biology. It has become increasingly clear over the past two decades or so that water is not simply life’s passive solvent, but is an active and versatile matrix that engages and interacts with biomolecules in complex, subtle, and essential ways. Most dramatically, it affects the structure, dynamics, folding and unfolding, interactions and functions of proteins. Moreover, the structure and dynamics of protein hydration shells seem to feed back onto those aspects of the biomolecules themselves, so that biological function depends on a delicate interplay between what we have previously regarded as distinct entities: the molecule and its environment. A fundamental understanding of the properties of water at biological interfaces is also important for many practical issues, including environmental problems and technologies for desalination, purification and waste water recovery.
The workshop provides an excellent opportunity for researchers from different disciplines to review the latest progress on interfacial biological water, and exchange their experience, progress and ideas.
Chair: Philip Ball, Nature, 4-6 Crinan Street, London N1 9XW, U.K.
Co-Chair: Haiping Fang, Shanghai Institute of Applied Physics, CAS, Shanghai
Secretary: Shenfu Chen, Zhejiang University
Xiaoling Lei, Shanghai Institute of Applied Physics, CAS, Shanghai
Organizing Committee
1. Enge Wang, Institute of Physics, CAS, China
2. Xiangyang Liu, National University of Singapore, Singapore
3. Ruhong Zhou, IBM Watson and Columbia University, USA
4. Jichen Li, University of Manchester, UK
5. Yuhong Xu, Shanghai Jiao Tong University, China
6. Jun Hu, Shanghai Institute of Applied Physics, CAS, China
7. Fengshou Zhang, Beijing Normal University, China
8. Gang Pan, State Key Laboratory of Environment Aquatic Chemistry, CAS, China
9. Shaoping Deng, Zhejiang Gongshang University, China
10. Shenfu Chen, Zhejiang University
Workshop on Water at Biological Interfaces
Hangzhou Water08
Oct. 27-28, 2008, Hangzhou, China
http://www.sinap.ac.cn/water08/index.html
First Announcement & Call for papers
Hangzhou Water08 is sponsored by the Shanghai Institute of Applied Physics (SINAP), cosponsored by the Zhejiang University, Organized by Shanghai Institute of Applied Physics, Chinese Academy of Sciences, and supported by National Science Foundation of China and the Chinese Academy of Science, and Ministry of Science and Technology of the People’s Republic of China
Water at biological interfaces plays a crucial role in cell and molecular biology. It has become increasingly clear over the past two decades or so that water is not simply life’s passive solvent, but is an active and versatile matrix that engages and interacts with biomolecules in complex, subtle, and essential ways. Most dramatically, it affects the structure, dynamics, folding and unfolding, interactions and functions of proteins. Moreover, the structure and dynamics of protein hydration shells seem to feed back onto those aspects of the biomolecules themselves, so that biological function depends on a delicate interplay between what we have previously regarded as distinct entities: the molecule and its environment. A fundamental understanding of the properties of water at biological interfaces is also important for many practical issues, including environmental problems and technologies for desalination, purification and waste water recovery.
The workshop provides an excellent opportunity for researchers from different disciplines to review the latest progress on interfacial biological water, and exchange their experience, progress and ideas.
Chair: Philip Ball, Nature, 4-6 Crinan Street, London N1 9XW, U.K.
Co-Chair: Haiping Fang, Shanghai Institute of Applied Physics, CAS, Shanghai
Secretary: Shenfu Chen, Zhejiang University
Xiaoling Lei, Shanghai Institute of Applied Physics, CAS, Shanghai
Organizing Committee
1. Enge Wang, Institute of Physics, CAS, China
2. Xiangyang Liu, National University of Singapore, Singapore
3. Ruhong Zhou, IBM Watson and Columbia University, USA
4. Jichen Li, University of Manchester, UK
5. Yuhong Xu, Shanghai Jiao Tong University, China
6. Jun Hu, Shanghai Institute of Applied Physics, CAS, China
7. Fengshou Zhang, Beijing Normal University, China
8. Gang Pan, State Key Laboratory of Environment Aquatic Chemistry, CAS, China
9. Shaoping Deng, Zhejiang Gongshang University, China
10. Shenfu Chen, Zhejiang University
Thursday, June 26, 2008
More Hofmeister headaches
The debate rumbles on over Hofmeister effects. In a paper in Scholarly Research Exchange [doi:10.3814/2008/761829 – paper here], Terence Evens and Randall Niedz of the US Horticultural Research Laboratory in Florida say that many previous studies of ion-specific effects on protein precipitation are flawed because they fail to take into account the dependence of pH on the type and concentration of ions in solution, treating it as an independent variable. More generally, they say that individual ion effects can’t be deduced in any straightforward way from the effects of specific salts. In a nutshell, this seems to be the key message: ‘Is the sulphate ion more effective at protein precipitation than the chloride ion? It depends on the protein. It depends on protein concentration. It depends on the concentration of the respective ions. It depends on the proportions and concentrations of the other cations and anions in solution. It depends on the dissolved gases. It may or may not depend on the pH. It depends on temperature. These dependencies are conflated, confounded, lost or ignored in traditional Hofmeister series, but are fundamentally essential to realizing a deeper understanding of ion-specific effects.’ Discuss, as they say. It’s certainly a rather discouraging message on what is already a bewildering problem, but Evens and Niedz present results for ovalbumin and BSA that seem to bear out this complexity.
In a related vein, Shekhar Garde and colleagues at RPI have examined the thermodyanmcis of hydrophobic hydration, association and folding for a hydrophobic polymer in sodium chloride solution and aqueous trimethylamine oxide (TMAO), an osmolyte [M. V. Athawale et al., J. Phys. Chem B 112, 5661; 2008 – paper here]. They’ve found previously that NaCl weakens hydrophobic hydration and enhances association, while TMAO has little effect (Ghosh et al., J. Phys. Chem. B 109, 642; 2005 and Athawale et al., Biophys. J. 89, 858; 2005). Here they carry out temperature-dependent simulations to figure out if the effects are entropic or enthalpic. For TMAO, there is almost precise enthalpic-entropic compensation. For NaCl, changes in solvent-solvent, solvent-salt and salt-salt energy lead to a dominant enthalpic contribution at small length scales (that is, for small solutes), but the strengthening of hydrophobic interactions is entropic in origin at large length scales, being governed by the need to form a solvent-solute interface. This seems to offer further evidence that there is no single ‘explanation’ of Hofmeister-type effects.
Meanwhile, Agustín Colussi and colleagues at Caltech have returned to a more basic level of the problem: the fractionation of ions at the air-water interface (a loose proxy for the air-hydrophobe interface) [J. Cheng et al., J Phys. Chem. B 112, 7157; 2008 – paper here]. They have shown previously [J. Cheng et al., J. Phys. Chem. B 110, 25598; 2006] that aggregation of anions at the interface seems to increase with increasing ion radius. They now extend their experimental study to the cases of the large anion PF6- and the highly polarizable IO3-, and look also at the effect of adding methanol, which will migrate to the surface and cap it with methyl groups. The same relationship with ion radius is found, and the fractionation barely depends on the methanol content. The authors conclude that this fractionation happens not because the ions have any affinity with the surface but because they are expelled from the bulk.
Now forget the salts. Esben Thormann and colleagues at the University of Southern Denmark have looked again at a familiar model system: a polystyrene particle several microns across stuck to an AFM tip and brought close to hydrophobic and hydrophilic surfaces [E. Thormann et al., Langmuir doi:10.1021/la8005162 – paper here]. For approaching surfaces in the hydrophilic case, all looks fine: the interactions are described by DLVO theory. But for the hydrophobic case, bridging air bubbles form, as has often been hypothesized, leading to jump-in at a separation of around 10 nm due to the action of the meniscus. When the particle is retracted, the bubble becomes elongated until it ruptures at about 70 nm. In both cases there are also force plateaus at separations of up to a few hundred nm, which the researchers interpret in terms of bridging polymer molecules pulled out from the particle surface. All this argues for caution in regarding the system as a model of the biological case.
Let’s stick with these model surfaces for a bit. Some time ago I mentioned some ‘curious’ results of Andrei Sommer and colleagues at the University of Ulm on irradiation of water films on diamond. I found some difficulty there figuring out what the underlying hypothesis was. Andrei has now sent me more material on this. The basic motivation for the work is the fact, known for some time but unexplained, that the surfaces of diamond are somewhat conductive. Andrei and colleagues believe this is due to proton migration in thin surface films of water, which are formed in humid conditions. Their experiments [A. P. Sommer et al., Cryst. Growth. Design 7, 2298; 2007] show that for hydrogen-terminated diamond, the conductivity drcreases with increasing humidity. They think this is because the highly ordered water films that form at low humidity are disrupted, degrading proton motion, as the films get thicker. This idea challenges the widely accepted model for the surface conductivity, called the transfer doping model [M. I. Landstrass & K. V. Ravi, Appl. Phys. Lett. 55, 975; 1989], which would predict increased conductivity with increased humidity. Andrei and colleagues have recently debated this point with John Angus and colleagues in Science [V. Chakrapani et al., Science 318, 1424; 2007].
From the perspective of water in biology, Andrei suggests the key point is that the highly ordered (indeed, essentially crystalline) water nanofilms he identifies on the (hydrophobic) diamond surface offer “a unique platform for the systematic investigation of nanoscopic water layers.” In a forthcoming paper for Crystal Growth and Design, he and his colleagues Dan Zhu and Hans Fecht argue that these layers might even provide a platform for the origin of life, as I understand it by potentially templating the evolution of organic monolayers. Apparently Albert Szent-Györgyi suggested something similar in the 1970s, proposing such a role for crystalline interfacial water layers. Diamonds can be extremely ancient, and also extraterrestrial. All this is very intriguing, although as someone now programmed to approach with scepticism the notion of enhanced ordering of water at hydrophobic surfaces I think I would like to see some more direct evidence that the water molecules on diamond are indeed truly ordered, especially if the claim is that this extends beyond a monolayer. But I think they’re working on that.
Heme catalases convert hydrogen peroxide to water and oxygen. One type of such enzyme, so-called Clade 3 of the most abundant (monofunctional) class, contains a tightly bound NADPH molecule which seems to protect one of the intermediates of the ferryloxo group against deactivation to a catalytically inactive form. Reiner Sustmann at Duisburg-Essen and colleagues propose in a new paper (W. Sicking et al., JACS 130, 7345-7356; 2008 – paper here) that a bound water molecule plays a critical part in this process, both by supplying a hydroxyl group that binds temporarily to the porphyrin group and then assists the fast two-electron reduction of the intermediate ferryloxo species by NADPH via a series of proton shifts, to restore the catalase resting state and avoid diversion of the reaction towards the deactivated state. A nice example of the multiple, sophisticated roles that bound water can play in active sites.
Lei Zhou and Steven Siegelbaum at Columbia University present a new coarse-grained approach for conducting normal-mode analysis of the dynamics of proteins, which has a lower computational cost than trying to extract the dynamics from a full MD simulation with explicit water [Biophys. J. 94, 3461; 2008 – paper here]. They say that this method is more accurate than are existing coarse-grained NMA techniques, and gives good agreement with experimental results from quasieleastic neutron and light scattering.
In my last blog entry I referred to recent work on the excited-state dynamics of the green fluorescent protein. Dan Huppert and colleagues at Tel Aviv University have looked at essentially the same aspect of the problem: the role of the proton-transfer process [R. Gepshtein et al., Langmuir 112, 7203; 2008 – paper here]. They say that the non-exponential dynamics seem to stem from the distance-dependence of the proton transfer between the chromophore and a bound water molecule that acts as the acceptor. This distance has a relatively large spread of about 0.2 angstroms in GFP.
Finally, thanks to everyone who helped make my Chem. Rev. article a most-accessed paper for the period Jan-Mar 2008.
In a related vein, Shekhar Garde and colleagues at RPI have examined the thermodyanmcis of hydrophobic hydration, association and folding for a hydrophobic polymer in sodium chloride solution and aqueous trimethylamine oxide (TMAO), an osmolyte [M. V. Athawale et al., J. Phys. Chem B 112, 5661; 2008 – paper here]. They’ve found previously that NaCl weakens hydrophobic hydration and enhances association, while TMAO has little effect (Ghosh et al., J. Phys. Chem. B 109, 642; 2005 and Athawale et al., Biophys. J. 89, 858; 2005). Here they carry out temperature-dependent simulations to figure out if the effects are entropic or enthalpic. For TMAO, there is almost precise enthalpic-entropic compensation. For NaCl, changes in solvent-solvent, solvent-salt and salt-salt energy lead to a dominant enthalpic contribution at small length scales (that is, for small solutes), but the strengthening of hydrophobic interactions is entropic in origin at large length scales, being governed by the need to form a solvent-solute interface. This seems to offer further evidence that there is no single ‘explanation’ of Hofmeister-type effects.
Meanwhile, Agustín Colussi and colleagues at Caltech have returned to a more basic level of the problem: the fractionation of ions at the air-water interface (a loose proxy for the air-hydrophobe interface) [J. Cheng et al., J Phys. Chem. B 112, 7157; 2008 – paper here]. They have shown previously [J. Cheng et al., J. Phys. Chem. B 110, 25598; 2006] that aggregation of anions at the interface seems to increase with increasing ion radius. They now extend their experimental study to the cases of the large anion PF6- and the highly polarizable IO3-, and look also at the effect of adding methanol, which will migrate to the surface and cap it with methyl groups. The same relationship with ion radius is found, and the fractionation barely depends on the methanol content. The authors conclude that this fractionation happens not because the ions have any affinity with the surface but because they are expelled from the bulk.
Now forget the salts. Esben Thormann and colleagues at the University of Southern Denmark have looked again at a familiar model system: a polystyrene particle several microns across stuck to an AFM tip and brought close to hydrophobic and hydrophilic surfaces [E. Thormann et al., Langmuir doi:10.1021/la8005162 – paper here]. For approaching surfaces in the hydrophilic case, all looks fine: the interactions are described by DLVO theory. But for the hydrophobic case, bridging air bubbles form, as has often been hypothesized, leading to jump-in at a separation of around 10 nm due to the action of the meniscus. When the particle is retracted, the bubble becomes elongated until it ruptures at about 70 nm. In both cases there are also force plateaus at separations of up to a few hundred nm, which the researchers interpret in terms of bridging polymer molecules pulled out from the particle surface. All this argues for caution in regarding the system as a model of the biological case.
Let’s stick with these model surfaces for a bit. Some time ago I mentioned some ‘curious’ results of Andrei Sommer and colleagues at the University of Ulm on irradiation of water films on diamond. I found some difficulty there figuring out what the underlying hypothesis was. Andrei has now sent me more material on this. The basic motivation for the work is the fact, known for some time but unexplained, that the surfaces of diamond are somewhat conductive. Andrei and colleagues believe this is due to proton migration in thin surface films of water, which are formed in humid conditions. Their experiments [A. P. Sommer et al., Cryst. Growth. Design 7, 2298; 2007] show that for hydrogen-terminated diamond, the conductivity drcreases with increasing humidity. They think this is because the highly ordered water films that form at low humidity are disrupted, degrading proton motion, as the films get thicker. This idea challenges the widely accepted model for the surface conductivity, called the transfer doping model [M. I. Landstrass & K. V. Ravi, Appl. Phys. Lett. 55, 975; 1989], which would predict increased conductivity with increased humidity. Andrei and colleagues have recently debated this point with John Angus and colleagues in Science [V. Chakrapani et al., Science 318, 1424; 2007].
From the perspective of water in biology, Andrei suggests the key point is that the highly ordered (indeed, essentially crystalline) water nanofilms he identifies on the (hydrophobic) diamond surface offer “a unique platform for the systematic investigation of nanoscopic water layers.” In a forthcoming paper for Crystal Growth and Design, he and his colleagues Dan Zhu and Hans Fecht argue that these layers might even provide a platform for the origin of life, as I understand it by potentially templating the evolution of organic monolayers. Apparently Albert Szent-Györgyi suggested something similar in the 1970s, proposing such a role for crystalline interfacial water layers. Diamonds can be extremely ancient, and also extraterrestrial. All this is very intriguing, although as someone now programmed to approach with scepticism the notion of enhanced ordering of water at hydrophobic surfaces I think I would like to see some more direct evidence that the water molecules on diamond are indeed truly ordered, especially if the claim is that this extends beyond a monolayer. But I think they’re working on that.
Heme catalases convert hydrogen peroxide to water and oxygen. One type of such enzyme, so-called Clade 3 of the most abundant (monofunctional) class, contains a tightly bound NADPH molecule which seems to protect one of the intermediates of the ferryloxo group against deactivation to a catalytically inactive form. Reiner Sustmann at Duisburg-Essen and colleagues propose in a new paper (W. Sicking et al., JACS 130, 7345-7356; 2008 – paper here) that a bound water molecule plays a critical part in this process, both by supplying a hydroxyl group that binds temporarily to the porphyrin group and then assists the fast two-electron reduction of the intermediate ferryloxo species by NADPH via a series of proton shifts, to restore the catalase resting state and avoid diversion of the reaction towards the deactivated state. A nice example of the multiple, sophisticated roles that bound water can play in active sites.
Lei Zhou and Steven Siegelbaum at Columbia University present a new coarse-grained approach for conducting normal-mode analysis of the dynamics of proteins, which has a lower computational cost than trying to extract the dynamics from a full MD simulation with explicit water [Biophys. J. 94, 3461; 2008 – paper here]. They say that this method is more accurate than are existing coarse-grained NMA techniques, and gives good agreement with experimental results from quasieleastic neutron and light scattering.
In my last blog entry I referred to recent work on the excited-state dynamics of the green fluorescent protein. Dan Huppert and colleagues at Tel Aviv University have looked at essentially the same aspect of the problem: the role of the proton-transfer process [R. Gepshtein et al., Langmuir 112, 7203; 2008 – paper here]. They say that the non-exponential dynamics seem to stem from the distance-dependence of the proton transfer between the chromophore and a bound water molecule that acts as the acceptor. This distance has a relatively large spread of about 0.2 angstroms in GFP.
Finally, thanks to everyone who helped make my Chem. Rev. article a most-accessed paper for the period Jan-Mar 2008.
Monday, June 16, 2008
A mixed bag
Michael Fayer and colleagues at Stanford have looked at how high salt concentrations and nanoconfinement alter orientational relaxation of water’s hydrogen-bonded network using ultrafast IR spectroscopy [S. Park et al., J. Phys. Chem. B 112, 5279-5290; 2008 – paper here.] They find that structural rearrangements of the network are slowed in 6M NaBr, but only moderately – by a factor around 3. The effects of confinement in reverse micelles can be more pronounced, being up to 20 times slower when the ‘nanopools’ of enclosed water are just 1.7 nm across. Moreover, the relaxation then becomes non-exponential. The effect seems to be due more to the effects of confinement per se than to interactions with the charged lipid head groups.
Jim Hynes and Damien Laage have a paper [J. Phys. Chem. B 10.1021/jp802033r] reporting an improved method for determining water residence times in hydration shells in MD simulations, which works with anything from ions to proteins. The key, it seems, is a better handling of the ‘tolerance time’, which relates to frustrated attempts of a water molecule to escape from the first hydration shell.
The spectrum of the green fluorescent protein of the Pacific jellyfish Aequorea Victoria, widely used in molecular biology as a marker, has several absorption bands that are interpreted as resulting from protonation and ionization of certain residues. The excited-state dynamics are thought to involve a proton relay involving three protons that can shuttle along a chain involving a bound water molecule. Ricard Gelabert of the Universitat Autònoma de Barcelona and colleagues have studied this process using a nuclear quantum dynamical simulation, and they find that proton transfer can be extremely fast in this system, initially happening in a matter of femtoseconds (but slowing down in the final stages). Moreover, the three protons seem to travel synchronously along the relay. The transfer induces a conformational change that breaks the relay, and thus is irreversible. The paper [O. Vendrell et al., J. Phys. Chem. B 112, 5500-5511; 2008] is here.
Nikolai Smolin and Valerie Daggett in Seattle have studied the mechanism of a so-called type III antifreeze protein from polar pout (Macrozoarces americanus) using simulations (J. Phys. Chem. B 112, 6193-6202; 2008 – paper here). They’re trying to figure out which of the various possible mechanisms for AFPs seems to apply here, and find that hydration waters on the protein’s ice-binding surface are more tetrahedral and ice-like than those elsewhere in the hydration sphere, suggesting that there is a good epitaxial match that promotes the binding of the protein to incipient ice crystals, preventing their further growth. I’d be interested to know if/how one might rule out the possibility that the protein could in fact provide a site for ice nucleation this way, preventing the growth of large crystals via a proliferation of small ones.
Sinan Keten and Markus Buehler at MIT have an interesting paper in Phys. Rev. Lett. (100, 198301; paper here) on the strength of protein folds secured purely by hydrogen-bonding. They use concepts from conventional fracture mechanics to look at the rupture of H-bonded beta-sheet-like folds, which enables them to conclude that protein domains stabilized this way can’t have rupture forces greater than about 200 pN.
A couple of papers in Langmuir look at the nature of the water-solid interface. Bill Ducker and colleagues have studied the formation of nanobubbles at hydrophobic surfaces, using total-internal-reflection IR spectroscopy to confirm that there are genuine gas-phase molecules present in both air and CO2 bubbles, some as small as just a few nm across to judge from the AFM images also presented (X. H. Zhang et al., Langmuir 24, 4756-4764; 2008 – paper here). The pressures are estimated at around 1-1.7 atm, but while the air bubbles can be stable for days, CO2 bubbles persist for only an hour or two. So while these nanobubbles are not ubiquitous on hydrophobic surfaces, they do form quite routinely.
And Sergio Acuna and Pedro Toledo in Chile have measured short-range forces between glass surfaces in water, using the AFM (Langmuir 24, 4881-4887; 2008 – paper here here). They find a repulsion at short distances (an intervening water film of 3-4 molecular layers) that does not depend on pH or on ion concentration or size. They say that the mechanism of silica hairs, proposed by Israelachvili and Wennerström (Nature 379, 219-225; 1996), can’t explain their data, and that the oscillatory forces they see are due to sequential squeezing out of water layers. I don’t fully understand what the authors mean by attributing this to the ‘creation of a hydrogen-bonding network at the surface level’ – whether this is different from the bulk, say, and why one need invoke hydrogen bonding at all as opposed simply to the kinds of steric packing effects that create oscillatory solvation forces in any solvent.
The paper on water dynamics in cells by Marion Jasnin, Joe Zaccai and colleagues that I mentioned earlier is now published in EMBO Reports, and is available here.
To those who’ve sent me material: I firmly intend to comment on it soon!
Jim Hynes and Damien Laage have a paper [J. Phys. Chem. B 10.1021/jp802033r] reporting an improved method for determining water residence times in hydration shells in MD simulations, which works with anything from ions to proteins. The key, it seems, is a better handling of the ‘tolerance time’, which relates to frustrated attempts of a water molecule to escape from the first hydration shell.
The spectrum of the green fluorescent protein of the Pacific jellyfish Aequorea Victoria, widely used in molecular biology as a marker, has several absorption bands that are interpreted as resulting from protonation and ionization of certain residues. The excited-state dynamics are thought to involve a proton relay involving three protons that can shuttle along a chain involving a bound water molecule. Ricard Gelabert of the Universitat Autònoma de Barcelona and colleagues have studied this process using a nuclear quantum dynamical simulation, and they find that proton transfer can be extremely fast in this system, initially happening in a matter of femtoseconds (but slowing down in the final stages). Moreover, the three protons seem to travel synchronously along the relay. The transfer induces a conformational change that breaks the relay, and thus is irreversible. The paper [O. Vendrell et al., J. Phys. Chem. B 112, 5500-5511; 2008] is here.
Nikolai Smolin and Valerie Daggett in Seattle have studied the mechanism of a so-called type III antifreeze protein from polar pout (Macrozoarces americanus) using simulations (J. Phys. Chem. B 112, 6193-6202; 2008 – paper here). They’re trying to figure out which of the various possible mechanisms for AFPs seems to apply here, and find that hydration waters on the protein’s ice-binding surface are more tetrahedral and ice-like than those elsewhere in the hydration sphere, suggesting that there is a good epitaxial match that promotes the binding of the protein to incipient ice crystals, preventing their further growth. I’d be interested to know if/how one might rule out the possibility that the protein could in fact provide a site for ice nucleation this way, preventing the growth of large crystals via a proliferation of small ones.
Sinan Keten and Markus Buehler at MIT have an interesting paper in Phys. Rev. Lett. (100, 198301; paper here) on the strength of protein folds secured purely by hydrogen-bonding. They use concepts from conventional fracture mechanics to look at the rupture of H-bonded beta-sheet-like folds, which enables them to conclude that protein domains stabilized this way can’t have rupture forces greater than about 200 pN.
A couple of papers in Langmuir look at the nature of the water-solid interface. Bill Ducker and colleagues have studied the formation of nanobubbles at hydrophobic surfaces, using total-internal-reflection IR spectroscopy to confirm that there are genuine gas-phase molecules present in both air and CO2 bubbles, some as small as just a few nm across to judge from the AFM images also presented (X. H. Zhang et al., Langmuir 24, 4756-4764; 2008 – paper here). The pressures are estimated at around 1-1.7 atm, but while the air bubbles can be stable for days, CO2 bubbles persist for only an hour or two. So while these nanobubbles are not ubiquitous on hydrophobic surfaces, they do form quite routinely.
And Sergio Acuna and Pedro Toledo in Chile have measured short-range forces between glass surfaces in water, using the AFM (Langmuir 24, 4881-4887; 2008 – paper here here). They find a repulsion at short distances (an intervening water film of 3-4 molecular layers) that does not depend on pH or on ion concentration or size. They say that the mechanism of silica hairs, proposed by Israelachvili and Wennerström (Nature 379, 219-225; 1996), can’t explain their data, and that the oscillatory forces they see are due to sequential squeezing out of water layers. I don’t fully understand what the authors mean by attributing this to the ‘creation of a hydrogen-bonding network at the surface level’ – whether this is different from the bulk, say, and why one need invoke hydrogen bonding at all as opposed simply to the kinds of steric packing effects that create oscillatory solvation forces in any solvent.
The paper on water dynamics in cells by Marion Jasnin, Joe Zaccai and colleagues that I mentioned earlier is now published in EMBO Reports, and is available here.
To those who’ve sent me material: I firmly intend to comment on it soon!
Wednesday, May 21, 2008
Effects of confinement
I have been feeling guilty at the slow pace with which I’ve been reading through a very nice preprint sent to me some time ago by Bob Eisenberg at Rush University Medical Center in Chicago, on the topic of how bubbles might act to gate ion channels. This brings together many recent ideas on how protein channels might be gated by evacuation of water from a hydrophobic pore – exactly the sort of thing discussed in the reviews by Gerhard Hummer et al. and Haiping Fang et al. in my previous post. The notion is that different channels have different mechanisms – mechanical, say, or voltage-depedent – to modulate the hydrophobicity of the channel and thus to cause an abrupt transition to a dewetted, capillary-evaporated state in which solutes are precluded from the channel. Eisenberg and colleagues present a general thermodynamic analysis of this process, and also offer the hypothesis that such a ‘bubble-induced’ mechanism might explain the anaesthetic effects of inert gases. The point is that the authors have now published the paper – or at least, what I assume is the same paper, as I’ve only so far seen the abstract – in Biophys. J. 94, 4282-4298 (2008) (paper here). Well worth looking at.
On the same general topic, Niharendu Choudhury in Mumbai has used MD simulations to look at how dewetting and capillary evaporation between two hydrophobic plates (close-packed paraffin monolayers) depends on the fine details of the plate structure (J. Phys. Chem. B 112, 6296-6300; 2008 – paper here). Specifically, he examines how the behaviour of the nano-confined water layer depends not only on plate separation but on the intermolecular distance in the paraffin plates, allowing a kind of ‘dilution’ of the hydrophobicity and solvent-surface dispersion forces. He finds that tuning this parameter can cause switches between wet, dry and intermittent wet/dry states, which might help to resolve differences seen in previous studies of this geometry. Moreover, the flickering formation and break-up of a water layer in the intermittent state can happen on nanosecond timescales, implying that simulations of protein hydration lasting only a few picoseconds may overlook important dynamical aspects of the problem.
Tobias Cramer at the University of Bologna and colleagues have looked at what one might consider the complementary problem: the spontaneous formation of a water bridge between two proximal surfaces (Langmuir 10.1021/la800220r – paper here). Their MD simulations examine how this process depends on an electric field across the gap, showing that there is a critical field strength at which the inhibitory influence of surface tension is overcome by electrostatic pressure. The focus here is mostly on scanning-probe-microscope-based experiments and technologies such as dip-pen nanolithography, but one can presumably imagine charging mechanisms for drawing water columns inside otherwise hydrophobic cavities in biomolecules. I have no idea whether such things are observed in nature…
There’s another take on nanoconfined water in a paper by Matthew Lane and colleagues at Sandia (J. M. D. Lane et al., Langmuir 24, 5209-5212; 2008 – paper here). They study the dynamics of a very thin film of water (submonolayer to bilayer) between two carboxyl-terminated alkanethiol self-assembled monolayers, using MD simulations. The diffusion coefficient of the water decreases as the layers become thinner, down to two orders of magnitude less than the bulk value, but the water remains liquid-like.
David Chandler, working with Adam Willard, has more on the role of solvent fluctuations in his dewetting model of hydrophobic assembly (discussed in earlier posts) in a paper in J. Phys. Chem. B 112, 6187-6192; 2008 (paper here). Fluctuations play a crucial role in the formation of a ‘vapour tunnel’ between two spherical hydrophobic particles, which draws them together. And in the same volume, Peter Rossky and colleagues expand on their work on the mechanism of protein cold denaturation, which I’ve also mentioned previously (C. F. Lopez et al., J. Phys. Chem. B 112, 5961-5967; 2008 – paper here).
Here’s another nice example of bound water playing a crucial role in enzyme function in a paper by Sason Shaik at the Hebrew University of Jerusalem and colleagues (Y. Wang et al., JACS 10.1021/ja711426y). They have looked at the mechanism by which cytochrome P450 StaP catalyses the formation of staurosporine, an antitumour agent, from chromopyrrolic acid. A critical step in this process is the abstraction of a proton from an N-H group on the substrate by an iron-oxo species in the enzyme. This seems to happen with the concerted assistance of two water molecules in the binding site: one shifts the proton onto a nearby histidine residue, and the other takes a proton from the other side of this residue’s side-chain and puts it on the iron-oxo group. Thus, the water molecules here form a hydrogen-bonded proton-relay network.
Rohit Pappu and colleagues at the University of St Louis in Missouri have an interesting study on the conformation of intrinsically disordered proteins, a class of protein that lack well defined 3D structures (H. T. Tran et al., JACS 10.1021/ja710446s – paper here). The common notion seems to be that because these proteins have sequences of low hydrophobicity, they are not tightly bound into compact structures by hydrophobic interactions. But IDPs are not totally random – they do have an ensemble of preferred conformational states. What creates them? The authors use simulations to conclude that these states are not dominated by specific intramolecular interactions in the polypeptide backbone, but from solvent-solute interactions, since water seems to be a generically poor solvent even for these low-hydrophobicity backbones.
More on hydration of poorly folded proteins comes from Supid Chakraborty and Sanjoy Bandyopadhyay at the Indian Institute of Technology in Kharagpur. They have used simulations to look at how the unfolding of the HP-36 subdomain of villin headpiece protein affects the dynamics of the hydration shell (J. Phys. Chem. B 112, 6500-6507; 2008 – paper here). Unfolding turns out to have a strong but quite complex effect on the rotational and translational motions of water in the hydration shell. It seems possible that there are knock-on effects: as one part of the protein unfolds, this can alter the structure and dynamics of hydration water around other segments in a cooperative manner. There’s clearly much more to be done on this interesting but under-investigated issue.
There’s more, as ever, to come when time permits…
On the same general topic, Niharendu Choudhury in Mumbai has used MD simulations to look at how dewetting and capillary evaporation between two hydrophobic plates (close-packed paraffin monolayers) depends on the fine details of the plate structure (J. Phys. Chem. B 112, 6296-6300; 2008 – paper here). Specifically, he examines how the behaviour of the nano-confined water layer depends not only on plate separation but on the intermolecular distance in the paraffin plates, allowing a kind of ‘dilution’ of the hydrophobicity and solvent-surface dispersion forces. He finds that tuning this parameter can cause switches between wet, dry and intermittent wet/dry states, which might help to resolve differences seen in previous studies of this geometry. Moreover, the flickering formation and break-up of a water layer in the intermittent state can happen on nanosecond timescales, implying that simulations of protein hydration lasting only a few picoseconds may overlook important dynamical aspects of the problem.
Tobias Cramer at the University of Bologna and colleagues have looked at what one might consider the complementary problem: the spontaneous formation of a water bridge between two proximal surfaces (Langmuir 10.1021/la800220r – paper here). Their MD simulations examine how this process depends on an electric field across the gap, showing that there is a critical field strength at which the inhibitory influence of surface tension is overcome by electrostatic pressure. The focus here is mostly on scanning-probe-microscope-based experiments and technologies such as dip-pen nanolithography, but one can presumably imagine charging mechanisms for drawing water columns inside otherwise hydrophobic cavities in biomolecules. I have no idea whether such things are observed in nature…
There’s another take on nanoconfined water in a paper by Matthew Lane and colleagues at Sandia (J. M. D. Lane et al., Langmuir 24, 5209-5212; 2008 – paper here). They study the dynamics of a very thin film of water (submonolayer to bilayer) between two carboxyl-terminated alkanethiol self-assembled monolayers, using MD simulations. The diffusion coefficient of the water decreases as the layers become thinner, down to two orders of magnitude less than the bulk value, but the water remains liquid-like.
David Chandler, working with Adam Willard, has more on the role of solvent fluctuations in his dewetting model of hydrophobic assembly (discussed in earlier posts) in a paper in J. Phys. Chem. B 112, 6187-6192; 2008 (paper here). Fluctuations play a crucial role in the formation of a ‘vapour tunnel’ between two spherical hydrophobic particles, which draws them together. And in the same volume, Peter Rossky and colleagues expand on their work on the mechanism of protein cold denaturation, which I’ve also mentioned previously (C. F. Lopez et al., J. Phys. Chem. B 112, 5961-5967; 2008 – paper here).
Here’s another nice example of bound water playing a crucial role in enzyme function in a paper by Sason Shaik at the Hebrew University of Jerusalem and colleagues (Y. Wang et al., JACS 10.1021/ja711426y). They have looked at the mechanism by which cytochrome P450 StaP catalyses the formation of staurosporine, an antitumour agent, from chromopyrrolic acid. A critical step in this process is the abstraction of a proton from an N-H group on the substrate by an iron-oxo species in the enzyme. This seems to happen with the concerted assistance of two water molecules in the binding site: one shifts the proton onto a nearby histidine residue, and the other takes a proton from the other side of this residue’s side-chain and puts it on the iron-oxo group. Thus, the water molecules here form a hydrogen-bonded proton-relay network.
Rohit Pappu and colleagues at the University of St Louis in Missouri have an interesting study on the conformation of intrinsically disordered proteins, a class of protein that lack well defined 3D structures (H. T. Tran et al., JACS 10.1021/ja710446s – paper here). The common notion seems to be that because these proteins have sequences of low hydrophobicity, they are not tightly bound into compact structures by hydrophobic interactions. But IDPs are not totally random – they do have an ensemble of preferred conformational states. What creates them? The authors use simulations to conclude that these states are not dominated by specific intramolecular interactions in the polypeptide backbone, but from solvent-solute interactions, since water seems to be a generically poor solvent even for these low-hydrophobicity backbones.
More on hydration of poorly folded proteins comes from Supid Chakraborty and Sanjoy Bandyopadhyay at the Indian Institute of Technology in Kharagpur. They have used simulations to look at how the unfolding of the HP-36 subdomain of villin headpiece protein affects the dynamics of the hydration shell (J. Phys. Chem. B 112, 6500-6507; 2008 – paper here). Unfolding turns out to have a strong but quite complex effect on the rotational and translational motions of water in the hydration shell. It seems possible that there are knock-on effects: as one part of the protein unfolds, this can alter the structure and dynamics of hydration water around other segments in a cooperative manner. There’s clearly much more to be done on this interesting but under-investigated issue.
There’s more, as ever, to come when time permits…
Friday, May 9, 2008
Ions and water at interfaces: will they be understood by August?
There has been a lot of debate, some described in earlier posts, about the behaviour of hydroxide and hydronium ions at air-water and hydrophobic interfaces. Some claim the air-water interface is acidic, others that it is basic. So do protons or hydroxide ions get preferentially adsorbed at these interfaces? I’ve been sent a preprint (now published in J. Phys. Chem. C, doi:10.1021/jp800888b; paper here) by Robert Vácha, Ronen Zangi, Jan Engberts and Pavel Jungwirth that casts new light on the issue with simulations of hydroxide hydration near hydrophobic walls in aqueous KOH. They find that rigid walls create strong layering effects and a peak of hydroxide concentration about 5Å from the wall. But when the wall atoms are allowed to vibrate thermally, and when the dispersion interactions are weaker (more like the air-water interface), this structuring tends to get washed out, in some cases completely. Thus it seems one can’t generalize about hydroxide adsorption (or not) at a hydrophobic interface.
Another blow to ‘water structure effects’ at interfaces comes from a paper by Mischa Bonn and colleagues, in Huib Bakker’s group at FOM Amsterdam (M. Sovago et al., Phys. Rev. Lett. 100, 173901; 2008 – paper here). They have investigated the double-peaked vibrational sum-frequency generation (VSFG) spectrum of the O-H bonds of interfacial water in the hydrogen-bonded region, at a lipid-water interface. The two peaks have previously been interpreted as two distinct classes of hydrogen bond, ‘weak’ (ice-like) and ‘strong’ (water-like). But the FOM team, along with others from the Universities of Amsterdam and Utrecht, have evidence from isotope substitution experiments that the double peak is due to vibrational coupling between stretching and bending modes. They therefore conclude that the interfacial water is more homogeneous than has been thought.
How ions affect hydration and hydrophobic interactions is one of the thorniest problems in this field, and I won’t repeat myself by trying to summarize what has been said previously on the issue. Suffice to say that this question is intimately bound up with the notoriously puzzling ion-specific Hofmeister effects on solubility and aggregation of proteins. Neither am I going to make a poor attempt at summarizing the conclusions of a new investigation into these phenomena by Roland Netz and colleagues in Germany and Sweden (D. Horinek et al., Langmuir 24, 1271-1283; 2008 – paper here). Let’s just say that they have used single-molecule AFM experiments and MD simulations to delve into the ion-specific factors, free from complications of bubble nucleation and cavitation that may intervene for extended surfaces. The punchline is that “the most important factor determining ion-specific adsorption at hydrophobic surfaces can best be described as surface-modified ion hydration” – but you’d best read the paper to unpack that. A useful addition to a complicated story.
Lawrence Pratt and coworkers have a preprint exploring the role of dispersion forces on the potential of mean force between methane molecules in water. The find that these attractive methane-water interactions contribute a repulsive term to the pair potential (potential of mean force, pmf) between methanes. They also say that packing effects in the hydration shells make a dominant contribution to this pmf, but not in a way that can be interpreted with a perturbative approach – that is (if I’ve understood this properly), by treating the pmf as a perturbation expansion around this basic term.
Haiping Fang of the Shanghai Institute of Applied Physics and his coworkers have a very nice ‘topical review’ entitled ‘Dynamics of single-file water chains inside nanoscale channels: physics, biological significance and applications’ in J. Phys. D: Appl. Phys. 41, 103002 (2008). Some of the same issues, and some others, are addressed in a recent review by Gerhard Hummer and colleagues: J. C. Rasaiah et al., ‘Water in nonpolar confinement: from proteins to nanotubes and beyond’, Ann. Rev. Phys. Chem. 59, 713-740 (2008).
Finally, a free advert for a RSC Faraday Division discussion meeting on 27-29 August at Heriot-Watt University in Edinburgh entitled ‘Water: From Interfaces to the Bulk’ (see details here.). The announcement says that this meeting “plans to achieve a unification of views towards the goal of understanding the microscopic structure and behaviour of condensed phases of water at interfaces and progressing into the bulk.” I wish I could be there.
Another blow to ‘water structure effects’ at interfaces comes from a paper by Mischa Bonn and colleagues, in Huib Bakker’s group at FOM Amsterdam (M. Sovago et al., Phys. Rev. Lett. 100, 173901; 2008 – paper here). They have investigated the double-peaked vibrational sum-frequency generation (VSFG) spectrum of the O-H bonds of interfacial water in the hydrogen-bonded region, at a lipid-water interface. The two peaks have previously been interpreted as two distinct classes of hydrogen bond, ‘weak’ (ice-like) and ‘strong’ (water-like). But the FOM team, along with others from the Universities of Amsterdam and Utrecht, have evidence from isotope substitution experiments that the double peak is due to vibrational coupling between stretching and bending modes. They therefore conclude that the interfacial water is more homogeneous than has been thought.
How ions affect hydration and hydrophobic interactions is one of the thorniest problems in this field, and I won’t repeat myself by trying to summarize what has been said previously on the issue. Suffice to say that this question is intimately bound up with the notoriously puzzling ion-specific Hofmeister effects on solubility and aggregation of proteins. Neither am I going to make a poor attempt at summarizing the conclusions of a new investigation into these phenomena by Roland Netz and colleagues in Germany and Sweden (D. Horinek et al., Langmuir 24, 1271-1283; 2008 – paper here). Let’s just say that they have used single-molecule AFM experiments and MD simulations to delve into the ion-specific factors, free from complications of bubble nucleation and cavitation that may intervene for extended surfaces. The punchline is that “the most important factor determining ion-specific adsorption at hydrophobic surfaces can best be described as surface-modified ion hydration” – but you’d best read the paper to unpack that. A useful addition to a complicated story.
Lawrence Pratt and coworkers have a preprint exploring the role of dispersion forces on the potential of mean force between methane molecules in water. The find that these attractive methane-water interactions contribute a repulsive term to the pair potential (potential of mean force, pmf) between methanes. They also say that packing effects in the hydration shells make a dominant contribution to this pmf, but not in a way that can be interpreted with a perturbative approach – that is (if I’ve understood this properly), by treating the pmf as a perturbation expansion around this basic term.
Haiping Fang of the Shanghai Institute of Applied Physics and his coworkers have a very nice ‘topical review’ entitled ‘Dynamics of single-file water chains inside nanoscale channels: physics, biological significance and applications’ in J. Phys. D: Appl. Phys. 41, 103002 (2008). Some of the same issues, and some others, are addressed in a recent review by Gerhard Hummer and colleagues: J. C. Rasaiah et al., ‘Water in nonpolar confinement: from proteins to nanotubes and beyond’, Ann. Rev. Phys. Chem. 59, 713-740 (2008).
Finally, a free advert for a RSC Faraday Division discussion meeting on 27-29 August at Heriot-Watt University in Edinburgh entitled ‘Water: From Interfaces to the Bulk’ (see details here.). The announcement says that this meeting “plans to achieve a unification of views towards the goal of understanding the microscopic structure and behaviour of condensed phases of water at interfaces and progressing into the bulk.” I wish I could be there.
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