Rearrangement of the water network hydrating a protein can provide a mechanism for allostery, according to a study by Peter Hamm and colleagues (B. Buchli et al., PNAS 10.1073/pnas.1306323110; paper here). They insert an azobenzene photoswitch in the binding groove of a PDZ domain protein, a common system for studying allostery, such that photo-induced isomerisation induces a conformational change similar to that which occurs on ligand binding. This enables them to use fast IR spectroscopy to look at the opening of the binding groove in a precisely controlled fashion, having first characterized the equilibrium structures using NMR. Their MD simulations show that a change in water density in the vicinity of the photoswitch right after switching propagates slowly through the water network over about 100 ns until it reaches the back of the protein. They suggest that this change in hydration structure could then induce, either dynamically or structurally, a remote allosteric change in protein conformation. In such a case, this would be a particularly dramatic example of how the hydration network is really a part of the functional apparatus of the protein.
How aquaporins transport water across membranes – and specifically how they do so without also transporting protons – has been a topic of much debate. The consensus has come to focus on the so-called NPA motif in the centre of the channel, a bottleneck through which water kolecules pass in single file, which seems to prohibit proton transport via electrostatic repulsion. Urszula Kosinska Eriksson at the University of Gothenburg and colleagues have recently reported a new high-resolution crystal structure of yeast aquaporin 1 which sheds new light on the issue (Science 340, 1346; 2013 – paper here). As Jeff Abramson and Armand Vartanian of ULCA explain in an accompanying perspective (Science 340, 1294 – paper here), the structure shows that proton transport isn’t (as some have suggested) blocked by hydrogen-bonding of a single water molecule in the NPA region to two asparagines. Rather, there are two independent waters here, but the interactions with the asparagines constrain their dynamics in such a way as to effectively break the ‘water wire’ threading through the channel. The authors say that water transport then seems to happen in pairwise fashion, similar to the ion transport in potassium channels – a possible example of convergent evolution to solve related problems.
A carefully structured water cluster also seems to play an important role in oxygen evolution during the photocycle of photosystem II, as Brandon Polander and Bridgette Barry of Georgia Tech deduce using laser flashes to induce the process and following it by FTIR spectroscopy (PNAS 10.1073/pnas1306532110 – paper here). The hydrogen-bonded cluster of five water molecules, bound to the catalytic Mn4CaO5 cluster, seems to become protonated during the S1→S2 part of the cycle, and it stores the proton until a later stage of the reaction. Ammonia can poison the reaction by disrupting the water cluster.
Water molecules that gain access to the interiors of globular proteins can act as probes of the intrinsic conformational dynamics that enable proteins to function. These waters in the ‘dry’ protein interior have been studied by magnetic relaxation dispersion spectroscopy, but atomistic models are needed to interpret those results. The problem is that such deep water penetration tends to be a rare event, demanding very long (millisecond) run times for simulations. A technique has recently been developed that enables this (D. E. Shaw et al., Science 330, 341; 2010), and now Filip Persson and Bertil Halle at Lund have used the method to compare MD with the MRD experiments for bovine pancreatic trypsin inhibitor (JACS 135, 8735; 2013 – paper here). They find that some of these internal hydration sites have water residence times of several microseconds, and that the water molecules gain access along single-file hydrogen-bonded chains.
Dewetting transtions are known to be important for at least some instances of hydrophobic assembly, and Bruce Berne and colleagues at Columbia now extend their earlier studies of dewetting-induced protein collapse to look at the potential role of such transitions in the docking of hydrophobic ligands in their binding pockets (J. Mondal et al., preprint http://www.arxiv.org/abs/1305.7505). In this way the solvent dynamics, which are retarded in the concave cavity, are explicitly included in the kinetics of the binding process – the process can be parametrized through a state variable that describes whether the pocket is ‘wet’ or ‘dry’, while the ligand diffuses across a potential-energy surface that can switch between these two states.
Daniel Sindhikara and Fumio Hirata of the Ritsumeikan University in Japan present a fast algorithm, based on the three-dimensional reference interaction site model (3D-RISM), for calculating the solvent distribution around solutes (J. Phys. Chem. B 117, 6718; 2013 – paper here). This is a wholly theoretical approach derived from the Ornstein-Zernicke equation. They say that it gives water positions and orientations that agree well with available experimental data, and demonstrate its use on HIV-1 protease.
Paul Ben Ishai at the Hebrew University of Jerusalem and colleagues have used quasielastic neutron scattering to look at salt effects on water dynamics (J. Phys. Chem. B 117, 7724; 2013 – paper here). They find that water diffusion is slower than in pure water, on average, in NaCl solution, but faster in KCl. They interpret the result in terms of structure-making and –breaking, saying that the disruption of the hydrogen-bonding network by potassium ions accounts for its apparent ‘lubricating’ effect.
The hydration state of arginine side chains can be deduced from its UV resonance-enhanced Raman spectrum, according to Sanford Asher at Pittsburgh and colleagues (Z. Hong et al., J. Phys. Chem. B 117, 7145; 2013 – paper here). Their density-functional calculations show that a particular vibration of this residue is sensitive to hydration. They use this signal to characterize differing degrees of hydration of Arg in two polyAla model peptides.