What a beautiful crystal structure is reported by Yasufumi Umena of Osaka City University and colleagues in Nature (473, 55; 2011 – paper here). They have revealed the entire photosystem II complex at 1.9 Å resolution, showing the hydration structure of the core Mn4CaO5 cluster along with the locations of 1,300 water molecules in a hydration shell that seems to offer several hydrogen-bonded channels for protons, water molecules for photolysis, or oxygen molecules. The latter are probably formed by oxidation of some of the four waters bound to the Mn cluster. I don’t recall ever seeing before such a complex, orchestrated and carefully rationalized example of a multifunctional hydration structure.
Collagen is generally considered a structural protein, but particular collagen motifs are also recognized as substrates by collagen binding proteins such as adhesins in some human pathogens. On the basis of MD simulations and comparison with crystal structures, Luigi Vitagliano at the Consiglio Nazionale delle Ricerce in Naples and colleagues say that the regions of collagen-binding adhesin CNA involved in binding to hydrophobic parts of the collagen triple helix are inherently prone to dewetting, making them primed to bind their target by reducing the desolvation penalty (Vitagliano et al., Biophys. J. 100, 2253-2261; 2011 – paper here). Moreover, besides these hydrophobic contacts the interaction between CNA and collagen is mediated by an intricate network of 13 water molecules.
Local water densities around biological systems can be calculated fairly accurately with a computationally cheap interaction-site model (based on the Ornstein-Zernicke integral equation), rather than with a full MD simulation, according to a new study by Vijay Pande at Stanford and colleagues, who compare the two for the hydration of GroEL (M. C. Stumpe et al., J. Phys. Chem. B 115, 319; 2011 – paper here).
In drug design, the surfaces of target proteins are often mapped out to look for ‘hot spots’ where it is particularly advantageous to place functional groups in the ligand complementary to those on the protein. This process often identifies many such local minima in a rugged potential-energy surface. But that’s in vacuo for a rigid surface. One might expect that including the protein’s conformational flexibility and interactions with water will smooth out this rugged landscape. But Katrina Lexa and Heather Carlson at the University of Michigan say that it doesn’t, unless the protein is allowed its full flexibility (JACS 133, 200; 2011 – paper here). In other words, there are no short cuts: if the molecule is semi-rigid, spurious hot spots remain.
Structured water molecules bound within cytochrome c have been suspected for some time of participating in the enzyme’s electron-transfer and oxygen reduction reactions, but it hasn’t been clear exactly how. Amandine Maréchal and Peter Rich at University College London have used FTIR spectroscopy to investigate the issue (PNAS pnas.1019419108 – paper here). They find that rearrangements of up to 8 water molecules are associated with the photolysis reaction, probably forming transient hydrogen-bonded pathways for proton conduction and gating.
More roles for water in protein-ligand binding are revealed by Michelle Sahai and Philip Biggin at Oxford (J. Phys. Chem. B 10.1021/jp200776t – paper here). They consider how the GluA2 ionotropic glutamate receptor binds both glutamate and the related compound AMPA, and find two quite distinct modes of binding. The difference seems to be in the location of a single water molecule in the binding cleft. They use density functional theory to figure out why it is more favourable for the water to sit in different positions in the two different cases. That they don’t seem yet to have fully settled that question (they cannot consider entropic contributions) seems to underline how tricky it might be to use bound waters in rational drug design.
Joe Dzubiella in Berlin has an interesting preprint on the thermodynamics of hydrophobic association which claims that the curvature of the interface is important. He points out how there seems to be a crossover at small size scales (about 1 nm) between enthalpy-driven hydrophobic association at larger scales and entropy-driven at smaller scales. But for concave binding cavities this does not seem to apply: enthalpy continues to dominate even at very small scales. Joe explains this on the basis that the surface-area-based models used to describe large-scale interactions on the basis of solvent-accessible area and surface tension remain applicable at small scales so long as “the antagonistic effects on concave vs. convex bending on water interface thermodynamics are properly taken into account”. The paper will appear in a forthcoming special issue of J. Stat. Phys. dedicated to water.
There’s a nice potted summary of current understanding of antifreeze protein ice-binding mechanisms by Kim Sharp of the University of Pennsylvania in PNAS (pnas.1104618108 – paper here). It is a commentary on a new study by Garnham et al. (PNAS pnas.1100429108), which I haven’t yet got hold of. They report the crystal structure of the AFP of an Antarctic bacterium, Marinomonas primoryensis, which has a new binding motif, a parallel beta-helix. This structure has the ice-binding surface fully solvent-exposed in the crystalline state, and so is likely to be “free from crystal-packing artifacts.” Much of this surface is hydrophobic (although anchored at the edges by H-bonds), and the claim is that this induces a clathrate-like structure in the first hydration layer that is close to the structure of ice – in other words, the AFP “brings its own ‘ice’ with it”.
With an eye on the Lum/Chandler/Weeks model of hydrophobic attraction, Pablo Debenedetti and colleagues have calculated the evaporation length scale – the separation of solvophobic plates at which capillary evaporation occurs – for water and a range of organic liquids (C. A. Cerdeiriña et al., J. Phys. Chem. Lett. 2, 1000; 2011 – paper here). There’s nothing conceptually new here, but the numbers are somewhat surprising: for water they find a length scale of about 1.5 microns at atmospheric pressure, which is much larger than I’d have expected. However, this applies for purely repulsive surfaces (contact angle of 180 degrees), which is of course rarely found, and never for protein surfaces. The length is also large for the organics, such as benzene, heptane and cyclohexane, but about a factor of 3 less so – water is (somewhat) anomalous here because of its large surface tension.
Hydration seems to respond to the flexibility of alicyclic systems, according to Annalisa Boscaino and Kevin Naidoo of the University of Cape Town in South Africa (J. Phys. Chem. B 10.1021/jp110248j – paper here). They find from MD simulations that molecules with a cyclopyranose framework, such as glucose, have a significantly higher hydration number than those based on a cyclohexane framework with hydroxyls, such as cyclohexanol. This seems to result from the greater rigidity of the former, enabling the formation of longer-lived hydrogen bonds to the surrounding water.
It’s generally thought that rearrangements of the hydrogen-bond network in bulk water must have a collective character. Andrei Tokmakoff at MIT and colleagues now provide evidence of that (R. A. Nicodemus et al., J. Phys. Chem. B 115, 5604; 2011 – paper here). They have used ultrafast IR spectroscopy of HOD in pure water to measure the energy barriers to spectral diffusion and reorientational relaxation, and find that the slow-decay component is consistent with collective reorganization.
Marcus Weinwurm and Christoph Dellago have calculated the vibrational spectra of single-file water molecules in narrow pores, enabling them to distinguish it from the stacked-ring structure in wider pores (J. Phys. Chem. B 115, 5268; 2011 – paper here).