First, an historical note: I recently discovered that this very nice paper by Charles Tanford on the history of the hydrophobic effect is available online. Much of this stuff appears in his books The Hydrophobic Effect (Wiley, 1980) and Nature’s Robots (OUP, 2001), but it’s a very nice summary of it.
Joe Zaccai has sent me a preprint of a paper just accepted by EMBO Reports that uses neutron scattering to look at water dynamics in vivo in E. coli. It shows that these dynamics are ‘normal’ and bulk-like, contrary to suggestions that water is ‘tamed’ in the cytoplasm. Bertil Halle and his coworkers have a paper in press with PNAS that reports precisely the same conclusion based on NMR data. So together, these papers ought to bury one more water myth.
There’s an interesting study here (JACS 130, 2928-2929; 2008) by Robert Ben and colleagues at Ottawa of the effect of sugar hydration on the antifreeze behaviour of glycoproteins. By substituting various sugars on antifreeze glycoprotein analogues, they find that the sugar conformation and thus hydration is important for inhibition of ice recrystallization. Here’s the punchline: “our data indicate that the compatibility of a hexose with the three-dimensional hydrogen-bonded network of water is inversely proportional to recrystallization-inhibition activity” – a finding they associate with the consequent free-energy change of transferring a water molecule to the ice lattice.
Also in JACS (130, 3120-3126; paper here), Greg Voth and his coworkers Feng Wang and Sergei Izvekov report ab initio MD simulations showing that hydronium ions form unusual cation pairs in concentrated aqueous HCl, stabilized by delocalization of the excess charge of the hydrated proton. This is consistent with Greg’s earlier work showing that hydronium seems to display amphiphilic behaviour – one can regard this as a kind of amphiphilic clustering.
Water does interesting stuff around benzene, which is hydrophobic around the edges but can form hydrogen bonds via the pi orbitals over the ring faces. So how does this translate to C60? Dahlia Weiss, Tanya Raschke and Michael Levitt have addressed that question using MD simulations in a paper here (J. Phys. Chem. B 112, 2981-2990; 2008). They say that the waters in the first hydration shell become more oriented, and have an increased number of hydrogen-bonding contacts, but that hydrogen bonding is disrupted between the first and second hydration shells. In general, the hydration shell is dense and ‘well-structured’ – I’d guess consistent, at a glance, with the kinds of orientational ordering described by Jan Engberts and W. Blokzijl in their 1993 article on hydrophobicity (Angew. Chem. Int. Ed. 32, 1545-1579), as opposed to the old notion of a hydrophobic ‘iceberg’. In this regard, the authors say that “C60 behaves as a large hydrophobic solute.”
Tuesday, March 11, 2008
Tuesday, March 4, 2008
Solvent not included
I talked a little bit in my review article about the difficulty of understanding and/or predicting the energetics of water expulsion from the active site of a protein when it binds its ligand, and the potential value of being able to do so for drug design. Richard Friesner, Bruce Berne and their colleagues have now reported a computational model which they say allows them to make this calculation in an efficient manner (JACS 130, 2817-2831; 2008 – paper here). They test it out on ligand binding in factor Xa, a potential anti-thrombosis drug target. They imply that this approach, considering a molecularly resolved rather than a continuum solvent, is needed for accurate prediction of the significant contributions that such displacements can make to the binding energies.
There’s more on this issue by Anthony Davis and colleagues at Bristol (E. Klein et al., Angew. Chem. Int. Ed. 10.1002/anie.200704733; paper here), who look at the role of displaced water in binding of carbohydrates by synthetic receptors (which they argue to be good analogues of carbohydrate-binding proteins). They say that hydrophobic interactions – which I think means here the expulsion of water from hydrophobic-hydrophobic contacts – play a significant role in binding.
Also somewhat related is a paper by Ken Raymond and colleagues at Berkeley, who have probed the influence of solvation on supramolecular encapsulation processes (Leung et al., JACS 130, 2798-2805; 2008 – paper here). They look at the subtle compensation effects between enthalpic and entropic contributions to encapsulation free energy: in water, desolvation releases water molecules to form more hydrogen bonds in the bulk, which is enthalpically favourable but entropically not. They conclude that the primary driving force of encapsulation, in water and other polar protic solvents, is the rearrangement of the hydrogen-bonding network in the solvent.
A recent paper on segregation of hydronium ions at air-water (and by extension, hydrophobic) surfaces, claiming that these have elevated pH (Buch et al., PNAS 104, 7342; 2007) stirred up some controversy. Some others claim that in fact such water surfaces are enriched with hydroxide, not hydronium. Konstantin Kudin and Roberto Car have now looked at both cases, using ab initio molecular dynamics simulations (JACS doi:10.1021/ja077205t; paper here). They say that both hydroxide and hydronium act as amphiphiles at these interfaces, with one end even more hydrophilic than water and the other essentially hydrophobic. The effect is larger for hydroxide, which implies that these ions accumulate more readily at the surface, giving it a negative charge. That’s indeed what seems to be observed in practice, as James Beattie pointed out to me when I wrote about the Buch et al. paper. But the results also seem consistent with Greg Voth’s predictions that hydronium acts as an amphiphile (e.g M. K. Petersen et al., J. Phys. Chem. B 108, 14804; 2004).
It’s very heartening to see in such a prominent place (Science 319,1197-1198; 2008) Douglas Tobias and John Hemminger’s head-on challenge to the notion of generalized structure-making and structure-breaking of water as an explanation for Hofmeister (specific-ion) effects. Tobias and Hemminger’s piece is a perspective on two recent papers mentioned earlier on this blog (Smith et al., JACS 129, 13847; 2007 and Mancinelli et al., J.Phys. Chem. B 109, 13570; 2007). I won’t outline those papers again, but simply point out that they both, from different perspectives, highlighted shortcomings of the traditional picture. T&H point out that recent work on specific ion absorption or depletion at surfaces by Jungwirth, Saykally, Pegram and Record, Berne and others are beginning to point to a rather more complicated picture of electrolyte effects that has nothingto do with modifications of the bulk structure of water.
Julio Fernandez and colleagues (first author Lorna Dougan at Columbia) argue here (PNAS 105, 3185-3190; 2008) that the mechanical functions of proteins, which involve conformational changes, are highly sensitive to the solvent because of solvent bridges between parts of the polypeptide chain. This is consistent with earlier work by Jose Onuchic and collaborators on protein folding (e.g. PNAS 99, 685; 2002). Dougan et al. use single-molecule force spectroscopy on a repeating-sequence domain of titin, a component of muscle tissue, to study how stretching it out changes when the solvent is switched to deuterium oxide or glycerol. The results are consistent with simulations in which the solvent molecules bridge adjacent beta-strands in the unfolding transition state. For water, several bridges of one molecule each seem to be involved; for glycerol, with a longer hydrogen-bonding ‘reach’, this transition state corresponds to a wider strand separation. Here the unfolding is an intrinsic part of the protein’s biological role, but presumably the same considerations would be expected to apply to denaturation of globular proteins too.
Fengshou Zhang at the Beijing Normal University has sent me a preprint of his paper now published in Phys. Rev. Lett. 100, 088104 (2008), in which he and his colleagues report MD simulations of conformational changes in DNA brought about by changes in solvent. Specifically, they consider ‘modified water’ with a tetrahedral structure but with variable dipole moment, ranging from ‘over-polarized’ (relative towater) to under-polarized. In the former case the double-helical B form is maintained but becomes stiffer (smaller fluctuations); as polarity decreases, the A form becomes increasingly favoured. The authors relate this to changes in phosphate screening, which is effected mainly by solvent molecules in more polar solvents and by counterions in less polar ones. I’m interested that Ruth Lynden-Bell is thanked for discussions; Ruth has pioneered this notion of a kind of counterfactual exploration of water’s role in structural biology, as a way of investigating the notion of ‘fine-tuning’ of water in biology (or should it be, of biology in water?).
There’s more good stuff to come, but that’s enough for now. It is very nice to be getting sent these things...
There’s more on this issue by Anthony Davis and colleagues at Bristol (E. Klein et al., Angew. Chem. Int. Ed. 10.1002/anie.200704733; paper here), who look at the role of displaced water in binding of carbohydrates by synthetic receptors (which they argue to be good analogues of carbohydrate-binding proteins). They say that hydrophobic interactions – which I think means here the expulsion of water from hydrophobic-hydrophobic contacts – play a significant role in binding.
Also somewhat related is a paper by Ken Raymond and colleagues at Berkeley, who have probed the influence of solvation on supramolecular encapsulation processes (Leung et al., JACS 130, 2798-2805; 2008 – paper here). They look at the subtle compensation effects between enthalpic and entropic contributions to encapsulation free energy: in water, desolvation releases water molecules to form more hydrogen bonds in the bulk, which is enthalpically favourable but entropically not. They conclude that the primary driving force of encapsulation, in water and other polar protic solvents, is the rearrangement of the hydrogen-bonding network in the solvent.
A recent paper on segregation of hydronium ions at air-water (and by extension, hydrophobic) surfaces, claiming that these have elevated pH (Buch et al., PNAS 104, 7342; 2007) stirred up some controversy. Some others claim that in fact such water surfaces are enriched with hydroxide, not hydronium. Konstantin Kudin and Roberto Car have now looked at both cases, using ab initio molecular dynamics simulations (JACS doi:10.1021/ja077205t; paper here). They say that both hydroxide and hydronium act as amphiphiles at these interfaces, with one end even more hydrophilic than water and the other essentially hydrophobic. The effect is larger for hydroxide, which implies that these ions accumulate more readily at the surface, giving it a negative charge. That’s indeed what seems to be observed in practice, as James Beattie pointed out to me when I wrote about the Buch et al. paper. But the results also seem consistent with Greg Voth’s predictions that hydronium acts as an amphiphile (e.g M. K. Petersen et al., J. Phys. Chem. B 108, 14804; 2004).
It’s very heartening to see in such a prominent place (Science 319,1197-1198; 2008) Douglas Tobias and John Hemminger’s head-on challenge to the notion of generalized structure-making and structure-breaking of water as an explanation for Hofmeister (specific-ion) effects. Tobias and Hemminger’s piece is a perspective on two recent papers mentioned earlier on this blog (Smith et al., JACS 129, 13847; 2007 and Mancinelli et al., J.Phys. Chem. B 109, 13570; 2007). I won’t outline those papers again, but simply point out that they both, from different perspectives, highlighted shortcomings of the traditional picture. T&H point out that recent work on specific ion absorption or depletion at surfaces by Jungwirth, Saykally, Pegram and Record, Berne and others are beginning to point to a rather more complicated picture of electrolyte effects that has nothingto do with modifications of the bulk structure of water.
Julio Fernandez and colleagues (first author Lorna Dougan at Columbia) argue here (PNAS 105, 3185-3190; 2008) that the mechanical functions of proteins, which involve conformational changes, are highly sensitive to the solvent because of solvent bridges between parts of the polypeptide chain. This is consistent with earlier work by Jose Onuchic and collaborators on protein folding (e.g. PNAS 99, 685; 2002). Dougan et al. use single-molecule force spectroscopy on a repeating-sequence domain of titin, a component of muscle tissue, to study how stretching it out changes when the solvent is switched to deuterium oxide or glycerol. The results are consistent with simulations in which the solvent molecules bridge adjacent beta-strands in the unfolding transition state. For water, several bridges of one molecule each seem to be involved; for glycerol, with a longer hydrogen-bonding ‘reach’, this transition state corresponds to a wider strand separation. Here the unfolding is an intrinsic part of the protein’s biological role, but presumably the same considerations would be expected to apply to denaturation of globular proteins too.
Fengshou Zhang at the Beijing Normal University has sent me a preprint of his paper now published in Phys. Rev. Lett. 100, 088104 (2008), in which he and his colleagues report MD simulations of conformational changes in DNA brought about by changes in solvent. Specifically, they consider ‘modified water’ with a tetrahedral structure but with variable dipole moment, ranging from ‘over-polarized’ (relative towater) to under-polarized. In the former case the double-helical B form is maintained but becomes stiffer (smaller fluctuations); as polarity decreases, the A form becomes increasingly favoured. The authors relate this to changes in phosphate screening, which is effected mainly by solvent molecules in more polar solvents and by counterions in less polar ones. I’m interested that Ruth Lynden-Bell is thanked for discussions; Ruth has pioneered this notion of a kind of counterfactual exploration of water’s role in structural biology, as a way of investigating the notion of ‘fine-tuning’ of water in biology (or should it be, of biology in water?).
There’s more good stuff to come, but that’s enough for now. It is very nice to be getting sent these things...
Thursday, February 7, 2008
Some old, lots new
I seem somehow to have overlooked a couple of highly relevant review articles in my Chem. Rev. paper. One is Ken Dill’s piece on ‘Modeling water, the hydrophobic effect, and ion solvation’:
K. A. Dill, T. M. Truskett, V. Vlachy & B. Hribar-Lee, Annu. Rev. Biophys. Biomol. Struct. 34, 173-199 (2005).
(Get it here.)
The other is Martin Chaplin’s paper ‘Do we underestimate the importance of water in cell biology?’, which, as the title implies, provides a much briefer overview of most of the issues I discuss in my review and carries the same basic message:
M. F. Chaplin, Nature Rev. Mol. Cell Biol. 7, 861-866 (2006).
(Get it here.)
Apologies for these omissions.
Moving on to things new… David Chandler’s comments on the mechanism of dewetting-induced hydrophobic assembly in my last post are expanded on in some detail in a new paper (A. P. Willard & D. Chandler, J. Phys. Chem. B doi:10.1021/jp077186+). They argue that the motions of the hydrophobic solutes are such that the basic cavitation process to form the ‘vapour bridge’ can have zero activation energy.
One of my favourite papers of the moment comes from Martina Havenith at Bochum and colleagues (S. Ebbinghaus et al., PNAS 104, 20749-20752; 2007). They have used terahertz spectroscopy and MD simulations to probe the hydration layer around proteins, in particular to estimate how thick it is. They find that differences in correlated water motions, relative to the bulk, extend to more than 2 nm from the protein surface. It’s a remarkable and important demonstration of the extra ‘reach’ that solvation affords biological macromolecules, and really makes the case for why the hydration layer needs to be considered in some sense a part of the molecule it encompasses, making them fuzzy-edged entities with a sphere of influence that stretches well beyond the apparent surface.
Martina and her colleagues have also looked at how this solvation structure is altered by mutations and by pH (S. Ebbinghaus et al., JACS doi:10.1021/ja0746520; paper here). They find that a single mutation of the five-helix bundle lambda*[6-85], replacing a glutamine side chain with aromatic residues, significantly reduces the reach of the perturbation to the solvation water. This distance is also reduced when the wild-type protein is denatured at pH 2. It will be interesting to know if both are general effects, implying that proteins are somehow optimized to induce maximum restructuring of the solvent.
Bertil Halle has sent me a preprint of a paper just accepted in PNAS, in which he along with Johan Qvist and Monika Davidovic at Lund, and Donald Hamelberg at UCSD, report a wholly water-free large hydrophobic cavity in bovine beta-lactoglobulin. This cavity, called the calyx and acting as a binding site for fatty acids and other nonpolar ligands, has a volume of 315 cubic Å. The authors contrast this with the interior of carbon nanotubes, which is nominally hydrophobic but threaded by water chains. It shows just how amazingly dry nature can keep itself when the need arises.
Bertil also has a new paper) with Erik Persson describing how magnetic relaxation dispersion studies of water molecules buried inside proteins can provide a probe of ns- to ms-timescale protein dynamics (E. Persson & B. Halle, JACS 130, 1774-1787; 2008).
Talking of water in nanotubes, Hideki Tanaka and his colleagues at Okayama University have ised MD simulations to map out the complete phase diagram of water in nanotubes at atmospheric pressure for diameters up to 1.7 nm (D. Takaiwa et al., PNAS 105, 39-43; 2008; paper here). They find at least nine different ice phases, each apparently adapting to the confined space in a way that maximizes the number of hydrogen bonds. They say that the confined liquid water doesn’t show a density maximum above freezing point, and that it shrinks on freezing. Nor is freezing necessarily a first-order transition here. All a rather beautiful picture of how profoundly confinement can alter water’s properties.
There’s a curious paper in Langmuir (A. P. Sommer, A. Caron & H.-J. Fecht, Langmuir 24, 635-636; 2008) claiming that ‘ordered interfacial water’ near hydrophobic and hydrophilic surfaces can be tuned with laser light, and that the light causes an increase in fluidity, presumed (as far as I can make out) to be due to depletion of the ‘ordered’ layer, in the hydrophilic case. I’m left wondering whether there is really any direct evidence for ‘increased ordering’ in these interfacial layers, and what precisely that means here. Something interesting seems to be happening, but I don’t think it’s clear what it is.
Aizhuo Liu et al. in Michigan report what they call ‘bifurcated’ hydrogen bonds in proteins, using isotope substitution studied with NMR (A. Liu et al., JACS doi:10.1021/ja710114r). But as far as I can see, these are not the bifurcated hydrogen bonds postulated by Sciortino et al. to play a role in molecular mobility in the liquid state (Nature 354, 218; 1991), where one proton binds to two oxygens. Rather, what we have here are simply oxygen atoms linked to two protons via H-bonding. Can we clean up the terminology please?
A paper by Masahide Terazima at Kyoto and colleagues offers evidence for the role of hydrophobic interactions in light switching of the antirepressor AppA of Rhodobacter sphaeroides (P. Hazra et al., J. Phys. Chem. B 112, 1494-1501; 2008. This molecule forms a dimer when its photosensitive BLUF domain is activated by blue light, and this photoactivated state then represses expression of genes involved in photosynthesis. It’s a rather subtle example of hydration changes inducing a biological behaviour.
K. A. Dill, T. M. Truskett, V. Vlachy & B. Hribar-Lee, Annu. Rev. Biophys. Biomol. Struct. 34, 173-199 (2005).
(Get it here.)
The other is Martin Chaplin’s paper ‘Do we underestimate the importance of water in cell biology?’, which, as the title implies, provides a much briefer overview of most of the issues I discuss in my review and carries the same basic message:
M. F. Chaplin, Nature Rev. Mol. Cell Biol. 7, 861-866 (2006).
(Get it here.)
Apologies for these omissions.
Moving on to things new… David Chandler’s comments on the mechanism of dewetting-induced hydrophobic assembly in my last post are expanded on in some detail in a new paper (A. P. Willard & D. Chandler, J. Phys. Chem. B doi:10.1021/jp077186+). They argue that the motions of the hydrophobic solutes are such that the basic cavitation process to form the ‘vapour bridge’ can have zero activation energy.
One of my favourite papers of the moment comes from Martina Havenith at Bochum and colleagues (S. Ebbinghaus et al., PNAS 104, 20749-20752; 2007). They have used terahertz spectroscopy and MD simulations to probe the hydration layer around proteins, in particular to estimate how thick it is. They find that differences in correlated water motions, relative to the bulk, extend to more than 2 nm from the protein surface. It’s a remarkable and important demonstration of the extra ‘reach’ that solvation affords biological macromolecules, and really makes the case for why the hydration layer needs to be considered in some sense a part of the molecule it encompasses, making them fuzzy-edged entities with a sphere of influence that stretches well beyond the apparent surface.
Martina and her colleagues have also looked at how this solvation structure is altered by mutations and by pH (S. Ebbinghaus et al., JACS doi:10.1021/ja0746520; paper here). They find that a single mutation of the five-helix bundle lambda*[6-85], replacing a glutamine side chain with aromatic residues, significantly reduces the reach of the perturbation to the solvation water. This distance is also reduced when the wild-type protein is denatured at pH 2. It will be interesting to know if both are general effects, implying that proteins are somehow optimized to induce maximum restructuring of the solvent.
Bertil Halle has sent me a preprint of a paper just accepted in PNAS, in which he along with Johan Qvist and Monika Davidovic at Lund, and Donald Hamelberg at UCSD, report a wholly water-free large hydrophobic cavity in bovine beta-lactoglobulin. This cavity, called the calyx and acting as a binding site for fatty acids and other nonpolar ligands, has a volume of 315 cubic Å. The authors contrast this with the interior of carbon nanotubes, which is nominally hydrophobic but threaded by water chains. It shows just how amazingly dry nature can keep itself when the need arises.
Bertil also has a new paper) with Erik Persson describing how magnetic relaxation dispersion studies of water molecules buried inside proteins can provide a probe of ns- to ms-timescale protein dynamics (E. Persson & B. Halle, JACS 130, 1774-1787; 2008).
Talking of water in nanotubes, Hideki Tanaka and his colleagues at Okayama University have ised MD simulations to map out the complete phase diagram of water in nanotubes at atmospheric pressure for diameters up to 1.7 nm (D. Takaiwa et al., PNAS 105, 39-43; 2008; paper here). They find at least nine different ice phases, each apparently adapting to the confined space in a way that maximizes the number of hydrogen bonds. They say that the confined liquid water doesn’t show a density maximum above freezing point, and that it shrinks on freezing. Nor is freezing necessarily a first-order transition here. All a rather beautiful picture of how profoundly confinement can alter water’s properties.
There’s a curious paper in Langmuir (A. P. Sommer, A. Caron & H.-J. Fecht, Langmuir 24, 635-636; 2008) claiming that ‘ordered interfacial water’ near hydrophobic and hydrophilic surfaces can be tuned with laser light, and that the light causes an increase in fluidity, presumed (as far as I can make out) to be due to depletion of the ‘ordered’ layer, in the hydrophilic case. I’m left wondering whether there is really any direct evidence for ‘increased ordering’ in these interfacial layers, and what precisely that means here. Something interesting seems to be happening, but I don’t think it’s clear what it is.
Aizhuo Liu et al. in Michigan report what they call ‘bifurcated’ hydrogen bonds in proteins, using isotope substitution studied with NMR (A. Liu et al., JACS doi:10.1021/ja710114r). But as far as I can see, these are not the bifurcated hydrogen bonds postulated by Sciortino et al. to play a role in molecular mobility in the liquid state (Nature 354, 218; 1991), where one proton binds to two oxygens. Rather, what we have here are simply oxygen atoms linked to two protons via H-bonding. Can we clean up the terminology please?
A paper by Masahide Terazima at Kyoto and colleagues offers evidence for the role of hydrophobic interactions in light switching of the antirepressor AppA of Rhodobacter sphaeroides (P. Hazra et al., J. Phys. Chem. B 112, 1494-1501; 2008. This molecule forms a dimer when its photosensitive BLUF domain is activated by blue light, and this photoactivated state then represses expression of genes involved in photosynthesis. It’s a rather subtle example of hydration changes inducing a biological behaviour.
Tuesday, January 22, 2008
Updates to the review
Inevitably, my review article has sins of omission and miscomprehension. I hope to put these right as they are pointed out to me.
One of the more serious is that I attributed to Meyer et al. [PNAS 102, 6839; 2005] the observation that a long-ranged electrostatic attraction can be established between two plates coated with lipids due to delamination of the monolayer and the formation of charged patches. This observation was in fact first reported by Jacob Klein and his coworkers in Phys. Rev. Lett. 96, 038301 (2006) and J. Phys. Chem. B 109, 3832-3837 (2005), though that work was overlooked in the Meyer et al. paper.
David Chandler has explained to me in more detail what is involved in the dewetting transition that he has postulated to occur as hydrophobic surfaces come together [Lum et al., J. Phys. Chem. B 103, 4570; 1999]. This transition has a signature that has not been necessarily sought in some of the simulations of protein aggregation looking for this effect, for example those by Bruce Berne’s group. David says:
“Bruce Berne is doing fine work. The empirical results he has collected are significant, and they are instructive when viewed in context. Problems can arise when the context is misunderstood, as I think they have been in some of Bruce’s writings. Case in point is that the ‘de-wetting’ mechanism of hydrophobic collapse does NOT require the presence of a vapor bubble BEFORE the collapse occurs, though that chronology is what Bruce takes to be the signature of the effect. Rather, an extended hydrophobic surface creates a loose fluctuating water interface. When the surface attracts that interface, the average interface position is close to the surface (i.e., no ‘vapor’ is explicitly seen). But that’s the average. More significantly, because the surface is soft (i.e., can fluctuate with little free energy cost), it becomes possible for water to move aside and thus possible for two hydrophobic surface to collapse upon one another. Consistent with this statement is that ensembles of trajectories and free energy functions show that the ‘reaction’ coordinate for hydrophobic assembly of two extended hydrophobic surfaces, whether idealized or ‘realistic’, has a significant contributor from water dynamics. That effect is the story of de-wetting that I have been trying to explain in my papers. I don’t think subsequent work has demonstrated this idea to be of limited applicability, though I do think many folks have misinterpreted what I have said. In a nutshell: in the matter of what liquid water does to make things happen, it’s the fluctuations that matter.”
Other papers relevant to the general topic of water in molecular biology that have been brought to my attention are:
A. Y. Mulkidjanian & D. A. Cherepanov, “Probing biological interfaces by tracing proton passage across them”, Photochem. Photobiol. Sci. 5, 577-587 (2006)
A. Y. Mulkidjanian, J. Heberle & D. A. Cherepanov, “Protons @ interfaces: Implications for biological energy conversion”, Biochim. Biophys. Acta 1757, 913-930 (2006)
J. Dzubiella, J. M. J. Swanson & J. A. McCammon, “Coupling nonpolar and polar salvation free energies in implicit solvent models”, J. Chem. Phys. 124, 084905 (2006)
L.-T. Cheng, J. Dzubiella, J. A. McCammon & B. Li, “Application of the level-set method to the implicit salvation of nonpolar molecules”, J. Chem. Phys. 127, 084503 (2007)
X. Gong, J. Li, H. Lu, R. Wan, J. Li, J. Hu & H. Fang, “A charge-driven molecular water pump”, Nature Nanotechnol. 2, 709-712 (2007)
There is also a nice crop of new papers that I should mention:
S. Joseph & N. R. Aluru, “Why are carbon nanotubes fast transporters of water?”, Nano. Lett. doi:10.1021/nl072385q (2008) [the answer is attributed to the presence of a depletion layer of water at the interface with the nanotube wall]
C. F. Lopez, R. K. Darst & P. J. Rossky, “Mechanistic elements o protein cold denaturation”, J. Phys. Chem. B doi:10.1021/jp075928t (2008) [in a nutshell: “low temperature leads to solvent-induced packing effects at the protein surface, and this more favourable water-protein interaction in turn destabilizes the overall protein structure”]
M. Lagi, X. Chu, C. Kim, F. Mallamace, P. Baglioni & S.-H. Chen, “The low-temperature dynamic crossover phenomenon in protein hyration water: simulations vs experiments”, J. Phys. Chem. B doi:10.1021/jp710714j (2008) [more on the explanation for the 220K dynamical transition of proteins in terms of the residual influence of a liquid-liquid critical point, an idea developed previously by these authors]
H. Chen, Y. Moreau, E. Derat & S. Shaik, “Quantum mechanical/molecular mechanical study of mechanisms of heme degradation by the enzyme heme oxygenase: the strategic function of the water cluster”, J. Am. Chem. Soc. doi:10.1021/ja076679p (2008) [more on the roles of ‘bound water’ in enzymatic catalysis]
D. K. Hore, D. S. Walker & G. L. Richmond, “Water at hydrophobic surfaces: when weaker is better”, J. Am. Chem. Soc. doi:10.1021/ja0755616 (2008) [uses MD simulations to conclude that “the degree of water structuring in the immediate vicinity of the oil-water junction is highest when the hydrophobic phase is least polar”]
One of the more serious is that I attributed to Meyer et al. [PNAS 102, 6839; 2005] the observation that a long-ranged electrostatic attraction can be established between two plates coated with lipids due to delamination of the monolayer and the formation of charged patches. This observation was in fact first reported by Jacob Klein and his coworkers in Phys. Rev. Lett. 96, 038301 (2006) and J. Phys. Chem. B 109, 3832-3837 (2005), though that work was overlooked in the Meyer et al. paper.
David Chandler has explained to me in more detail what is involved in the dewetting transition that he has postulated to occur as hydrophobic surfaces come together [Lum et al., J. Phys. Chem. B 103, 4570; 1999]. This transition has a signature that has not been necessarily sought in some of the simulations of protein aggregation looking for this effect, for example those by Bruce Berne’s group. David says:
“Bruce Berne is doing fine work. The empirical results he has collected are significant, and they are instructive when viewed in context. Problems can arise when the context is misunderstood, as I think they have been in some of Bruce’s writings. Case in point is that the ‘de-wetting’ mechanism of hydrophobic collapse does NOT require the presence of a vapor bubble BEFORE the collapse occurs, though that chronology is what Bruce takes to be the signature of the effect. Rather, an extended hydrophobic surface creates a loose fluctuating water interface. When the surface attracts that interface, the average interface position is close to the surface (i.e., no ‘vapor’ is explicitly seen). But that’s the average. More significantly, because the surface is soft (i.e., can fluctuate with little free energy cost), it becomes possible for water to move aside and thus possible for two hydrophobic surface to collapse upon one another. Consistent with this statement is that ensembles of trajectories and free energy functions show that the ‘reaction’ coordinate for hydrophobic assembly of two extended hydrophobic surfaces, whether idealized or ‘realistic’, has a significant contributor from water dynamics. That effect is the story of de-wetting that I have been trying to explain in my papers. I don’t think subsequent work has demonstrated this idea to be of limited applicability, though I do think many folks have misinterpreted what I have said. In a nutshell: in the matter of what liquid water does to make things happen, it’s the fluctuations that matter.”
Other papers relevant to the general topic of water in molecular biology that have been brought to my attention are:
A. Y. Mulkidjanian & D. A. Cherepanov, “Probing biological interfaces by tracing proton passage across them”, Photochem. Photobiol. Sci. 5, 577-587 (2006)
A. Y. Mulkidjanian, J. Heberle & D. A. Cherepanov, “Protons @ interfaces: Implications for biological energy conversion”, Biochim. Biophys. Acta 1757, 913-930 (2006)
J. Dzubiella, J. M. J. Swanson & J. A. McCammon, “Coupling nonpolar and polar salvation free energies in implicit solvent models”, J. Chem. Phys. 124, 084905 (2006)
L.-T. Cheng, J. Dzubiella, J. A. McCammon & B. Li, “Application of the level-set method to the implicit salvation of nonpolar molecules”, J. Chem. Phys. 127, 084503 (2007)
X. Gong, J. Li, H. Lu, R. Wan, J. Li, J. Hu & H. Fang, “A charge-driven molecular water pump”, Nature Nanotechnol. 2, 709-712 (2007)
There is also a nice crop of new papers that I should mention:
S. Joseph & N. R. Aluru, “Why are carbon nanotubes fast transporters of water?”, Nano. Lett. doi:10.1021/nl072385q (2008) [the answer is attributed to the presence of a depletion layer of water at the interface with the nanotube wall]
C. F. Lopez, R. K. Darst & P. J. Rossky, “Mechanistic elements o protein cold denaturation”, J. Phys. Chem. B doi:10.1021/jp075928t (2008) [in a nutshell: “low temperature leads to solvent-induced packing effects at the protein surface, and this more favourable water-protein interaction in turn destabilizes the overall protein structure”]
M. Lagi, X. Chu, C. Kim, F. Mallamace, P. Baglioni & S.-H. Chen, “The low-temperature dynamic crossover phenomenon in protein hyration water: simulations vs experiments”, J. Phys. Chem. B doi:10.1021/jp710714j (2008) [more on the explanation for the 220K dynamical transition of proteins in terms of the residual influence of a liquid-liquid critical point, an idea developed previously by these authors]
H. Chen, Y. Moreau, E. Derat & S. Shaik, “Quantum mechanical/molecular mechanical study of mechanisms of heme degradation by the enzyme heme oxygenase: the strategic function of the water cluster”, J. Am. Chem. Soc. doi:10.1021/ja076679p (2008) [more on the roles of ‘bound water’ in enzymatic catalysis]
D. K. Hore, D. S. Walker & G. L. Richmond, “Water at hydrophobic surfaces: when weaker is better”, J. Am. Chem. Soc. doi:10.1021/ja0755616 (2008) [uses MD simulations to conclude that “the degree of water structuring in the immediate vicinity of the oil-water junction is highest when the hydrophobic phase is least polar”]
Saturday, December 22, 2007
Chem Rev article is now online
My review article on water in cell biology has now been published online in Chemical Reviews – it’s available here. Some minor corrections in the first five pages were omitted (I’m hoping these might yet be fixed), but such is life. Hope it’s useful.
Tuesday, December 11, 2007
Spherical water
More on the issue of urea denaturation of proteins comes from Paul Cremer and colleagues at Texas A&M (Chen et al., JACS 129, 15104; 2007). They have used vibrational sum frequency spectroscopy to look at the orientation of urea molecules at the surface of bovine serum albumin. They find that the orientation depends on the surface charge on the protein: it flips from pointing the amines towards the surface at high pH (negative surface charge) to pointing the carbonyls at low pH (positive surface charge). That’s interesting. But the authors’ argument that this supports an indirect model for denaturation, where the urea primarily acts via a restructuring of the hydration sphere rather than direct surface bonding, seems rather vague and not at all obvious at this point.
Sergey Buldyrev at Yeshiva University and coworkers (Kumar, Debenedetti, Rossky, Stanley) have found water-like behaviour in a rather un-water-like system (PNAS, doi:10.1073/pnas.0708427104). They’ve looked at a fluid of spherically symmetric particles with two interaction length scales – a hard core and a soft repulsive ‘ramp’ – and see water-like anomalies such as expansion on cooling, as well as cold-induced ‘denaturation’ of a hard-sphere polymer chain. This suggests that this dual-scale characteristic might be the most fundamental feature that gives water its ‘uniqueness’.
Ivan Brovchenko’s paper on water percolation effects in DNA polymorphism, which I mentioned several weeks back, has now been published in JACS: doi:10.1021/ja0732882.
Sergey Buldyrev at Yeshiva University and coworkers (Kumar, Debenedetti, Rossky, Stanley) have found water-like behaviour in a rather un-water-like system (PNAS, doi:10.1073/pnas.0708427104). They’ve looked at a fluid of spherically symmetric particles with two interaction length scales – a hard core and a soft repulsive ‘ramp’ – and see water-like anomalies such as expansion on cooling, as well as cold-induced ‘denaturation’ of a hard-sphere polymer chain. This suggests that this dual-scale characteristic might be the most fundamental feature that gives water its ‘uniqueness’.
Ivan Brovchenko’s paper on water percolation effects in DNA polymorphism, which I mentioned several weeks back, has now been published in JACS: doi:10.1021/ja0732882.
Tuesday, December 4, 2007
More water tuning, and out with the structure-breakers
I couldn’t hope for a better illustration of how biomolecular hydration can be used to fine-tune function than that provided in a paper in Science by Keith Hodgson at Stanford and coworkers (30 November, Vol. 318, p.1464). They have used sulphur XAS to look at the iron-sulphur sites in the high-potential iron-sulphur protein (HiPIP) and in ferredoxin (Fd). Both have much the same iron-sulphur cluster, yet that in HiPIP gets oxidized and that in Fd gets reduced at physiological potentials. The authors conclude that this difference is due to different degrees of Fe-S covalency, which in turn depends on the hydration state. In other words, function here has in some sense rather little to do with the protein’s primary structure, but depends instead on the hydration environment.
Maria Ricci in Rome and her colleagues have a great paper in J. Phys. Chem. (Vol. 111, p.13570) on the structure of NaCl and KCl solutions as deduced by neutron scattering. They find that K ions have more orientationally disordered hydration shells than Na ions, while Cl ions tend to form H-bonded bridges between waters. In both cases the H-bonded structure of water is significantly disrupted, but not in a way that yields to any simplistic description as ‘structure-making’ or ‘structure-breaking’. As a result, the authors say, those old ideas “are not helpful in understanding how these ions interact with water at the molecular level.” Hear, hear. Let’s hope that message gets out.
There’s what looks to be a very nice paper in Biophys. J. (Vol. 93, p.4116) from Bryan Patel, Pablo Debenedetti, Frank Stillinger and Peter Rossky on the way hydrophobic hydration acts to cause protein denaturation at low and high temps and at high pressure. I’ve only seen the abstract of this so far, but the comment that “an explicit treatment of hydrophobic hydration is sufficient to produce cold, pressure, and thermal denaturation” implies that this paper covers a lot of important ground in this controversial area.
In a paper in J. Phys. Chem. B (doi:10.1021/jp077110d), Julio Martinez and Pieter Stroeve suggests that they can resolve previously discrepant findings about the nature of the interface between water and a hydrophobic surface. They have used surface plasmon resonance to study this interface for a self-assembled monolayer, and report that it evolves slowly: at first, nanobubbles are formed, but these disappear after about 10 minutes. Equilibrium is not reached, however, until about 30 hours later. In this equilibrium state, there is apparently an ‘organic layer’ at the interface, by which they seem to mean a film of organic contaminants. Something like that was reported by Evans et al. in Physica A 339, 101 (2004). I’m not sure this will be the final word, or quite what it implies for hydrophobic interactions, but it does seem to offer a reason why previous results have differed.
There’s going to be more to be said too about the issue of ions at the air-water or hydrophobe-water surface. Pavel Jungwirth and coworkers made a small splash earlier this year with a PNAS paper that claimed to find surface acidification. Greg Voth predicted that some time ago (se below, ‘Acid on top’, http://waterinbiology.blogspot.com/2007_04_01_archive.html). But others insist that hydroxide ions preferentially segregate at the surface. Jan Engberts now tells me that “Jungwirth has now performed MD simulations, with the help of my previous post-doc Ronen Zangi, now at Columbia [with Bruce Berne]. And they largely reproduce our previous results, i.e. hydroxide binding....The idea is now to write a joint paper. I am not sure what comes out of it.” Watch this space… And meanwhile, Dominic Horinek and Roland Netz have a simulation paper in Phys. Rev. Lett. (Vol. 99, 226104) which reports that large, polarisable halide ions are adsorbed preferentially at the surface of a hydrophobic SAM.
Maria Ricci in Rome and her colleagues have a great paper in J. Phys. Chem. (Vol. 111, p.13570) on the structure of NaCl and KCl solutions as deduced by neutron scattering. They find that K ions have more orientationally disordered hydration shells than Na ions, while Cl ions tend to form H-bonded bridges between waters. In both cases the H-bonded structure of water is significantly disrupted, but not in a way that yields to any simplistic description as ‘structure-making’ or ‘structure-breaking’. As a result, the authors say, those old ideas “are not helpful in understanding how these ions interact with water at the molecular level.” Hear, hear. Let’s hope that message gets out.
There’s what looks to be a very nice paper in Biophys. J. (Vol. 93, p.4116) from Bryan Patel, Pablo Debenedetti, Frank Stillinger and Peter Rossky on the way hydrophobic hydration acts to cause protein denaturation at low and high temps and at high pressure. I’ve only seen the abstract of this so far, but the comment that “an explicit treatment of hydrophobic hydration is sufficient to produce cold, pressure, and thermal denaturation” implies that this paper covers a lot of important ground in this controversial area.
In a paper in J. Phys. Chem. B (doi:10.1021/jp077110d), Julio Martinez and Pieter Stroeve suggests that they can resolve previously discrepant findings about the nature of the interface between water and a hydrophobic surface. They have used surface plasmon resonance to study this interface for a self-assembled monolayer, and report that it evolves slowly: at first, nanobubbles are formed, but these disappear after about 10 minutes. Equilibrium is not reached, however, until about 30 hours later. In this equilibrium state, there is apparently an ‘organic layer’ at the interface, by which they seem to mean a film of organic contaminants. Something like that was reported by Evans et al. in Physica A 339, 101 (2004). I’m not sure this will be the final word, or quite what it implies for hydrophobic interactions, but it does seem to offer a reason why previous results have differed.
There’s going to be more to be said too about the issue of ions at the air-water or hydrophobe-water surface. Pavel Jungwirth and coworkers made a small splash earlier this year with a PNAS paper that claimed to find surface acidification. Greg Voth predicted that some time ago (se below, ‘Acid on top’, http://waterinbiology.blogspot.com/2007_04_01_archive.html). But others insist that hydroxide ions preferentially segregate at the surface. Jan Engberts now tells me that “Jungwirth has now performed MD simulations, with the help of my previous post-doc Ronen Zangi, now at Columbia [with Bruce Berne]. And they largely reproduce our previous results, i.e. hydroxide binding....The idea is now to write a joint paper. I am not sure what comes out of it.” Watch this space… And meanwhile, Dominic Horinek and Roland Netz have a simulation paper in Phys. Rev. Lett. (Vol. 99, 226104) which reports that large, polarisable halide ions are adsorbed preferentially at the surface of a hydrophobic SAM.
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