Apologies for the long silence. This blog is still active, but Christmas (among other things) got in the way and then I face the Sysiphean task of catching up. That task is not by any means completed here, but I want to flag up that Water in Biology hasn’t expired. Much more as soon as I can manage it.
Bruce Berne, Richard Friesner and Lingle Wang at Columbia have recently introduced the notion that ligand binding in protein receptor pockets is largely driven by the displacement of water molecules that sit in an unfavourable position in the pocket, which are replaced with groups on the ligand that are complementary to the protein surface (Young et al., PNAS 104, 808; 2007; Abel et al., JACS 130, 2817; 2008). In a new paper (Wang et al., PNAS 108, 1326; 2011 – paper here) they consider what their model, called WaterMap, has to say about regions of the binding pocket that are initially dry, being highly unfavourable environments for water. Including an interaction term in the model that represents the formation of a (hydrophobic) protein-ligand interface in dry regions, they can compute binding affinities in good agreement with experiment.
Dave Thirumalai at Maryland and his coworkers offer a striking view of how amyloid fibrils self-assemble from interdigitated beta-sheets (G. Reddy et al., PNAS 10.1073/pnas.108616107 – paper not yet online). They present a MD study of the association of beta-sheets in two amyloidogenic proteins of very different sequence, one polar and the other hydrophobic. They say that in the former case the association of the sheets is mediated by one-dimensional water wires at the interface between them, which are gradually expelled. But for the hydrophobic peptides the sheets come together in something like an abrupt drying transition, as postulated previously for some protein-folding and aggregation processes. This happens much faster (nearly 1,000-fold) than the previous case, since the trapped water wires for the polar peptide create a barrier to rapid assembly. Thus, although the final structures are very similar, the mechanisms and dynamics are quite different. It would seem that this paper ties in with a new one by Ken Dill and colleagues on the mechanisms of amyloid assembly into fibrils, of which I’ve only seen the abstract (which suggests that there’s not a big emphasis on the role of the solvent here beyond the involvement of hydrophobicity) (J. D. Schmit et al., Biophys. J. 100, 450-458; 2011 – paper here).
Cytochrome c oxidase (CcO) acts as a proton pump in which the transmembrane proton motion is thought to be facilitated by a proton wire involving strategically placed water molecules. The roles of these waters are investigated by Shelagh Ferguson-Miller and colleagues at Michigan State based on high-resolution crystals structures of two mutant forms of bacterial CcO (Liu et al., PNAS 108, 1284; 2011 – paper here). In both mutants, where proton transfer is inhibited to different degrees, the overall structural changes are very small but one or more of the bound waters is eliminated. The story is not, however, quite as simple as a mere break in the water wires, but involves subtle conformational changes between oxidized and reduced forms of the metal centres: an indication that, while bound water undoubtedly plays an active role in the catalytic function, in this case that role resists reduction to a simplistic picture.
Human telomeres contain G-rich sequences that form quadruplex structures in Hoogsteen hydrogen-bonded patterns. It’s not clear what influences the stability of this unusual motif, but John Trent and colleagues at the University of Louisville in Kentucky say that hydration plays a major part (M. C. Miller et al., JACS 132, 17105-17107; 2010 – paper here). They say that previous studies of the crystal structure of these sequences have been misleading because the dehydrating agents used to cause precipitation (PEGs) may give crystal structures that are not closely related to those in solution. Instead they use acetonitrile (which is water-soluble but does not engage in hydrogen-bonding) as the cosolvent for CD and NMR solution studies, and find that stabilization of the quadruplex seems to be caused more by dehydration than by steric crowding effects.
How hydration affects energy relaxation of cytochrome c after photoexcitation has been studied using ultrafast spectroscopy by Shuji Ye of the University of Science and Technology of China in Hefei and and Andrea Markelz of SUNY at Buffalo (J. Phys. Chem. B 114, 15151-15157; 2010 – paper here). One of the main conclusions is that hydration doesn’t in fact have a great deal of influence on the initial energy dynamics: there is an initial fast (around 300 fs) conversion from the electronically excited state to a vibrationally excited ground state, which is essentially hydration-independent. But the vibrational cooling then does involve interaction with the solvent, more or less in line with the existing notion that hydration water acts as a kind of plasticizer in this molecule.
Finally for now, and not really at all relevant to the real themes of this blog but too much of a curiosity for me to ignore, there are two papers on the arxiv investigating the notorious Mpemba effect, whereby hot water is said to sometimes freeze faster than cold: see here and here.