Tuesday, July 6, 2010

Water channels and flu resistance

What happens to hydrophobic interactions in the presence of charge? Bruce Berne and colleagues at Columbia have used MD simulations to explore that question (L. Wang et al., J. Phys. Chem. B 114, 7294-7301; 2010 – paper here). They find that the binding affinity of a hydrophobic particle to a hydrophobic plate, when it is placed between two such plates, is decreased if the plates are charged. Indeed, with increasing charge density the plates can become hydrophilic-like, expelling the particle from the interplate region.

Allan Friesen and Dmitry Matyushov at Arizona State University have considered the polarity of the interface between water and hydrophobic particles, which they model as hard spheres surrounded by a Lennard-Jones layer (arxiv.org/1004.1728 – paper here). (They call these particles, a little confusingly, ‘cavities’, presumably because they open up cavities in the solvent.) They find that there is a significant increase in the local polarity of the water at the interface, meaning that any charges in the solute particle are significantly screened. Moreover, dipolar relaxation in the first hydration shell is slowed significantly, with a relaxation time of around 50 ps.

Hirofumi Sato and colleagues at Kyoto University have used an approach called multicentre molecular Ornstein-Zernicke equation theory to calculate the hydration structure of bacteriorhodopsin (and a simpler serine coiled coil) (K. Hirano et al., J. Phys. Chem. B 114, 7935-7941; 2010 – paper here). I’ve not come across this method and don’t fully understand it – I’m rather surprised that a first-principles method like this, using the O-Z equation, can be applied to such a complex system. But given that it is 20 years since I last set eyes on the O-Z equation, it is very probable that I’m behind the times. In any event, the authors say that the solvent distribution they calculate agrees well with that found from XRD, and they can pull out the relative strengths of the hydrogen-bonding interactions, for example of the bound water molecules close to the Schiff base of bR.

The efficacy of the antiflu drug amantadine (AMT) is undermined by resistance that has been reported as developing in influenza A. A possible mechanism of resistance is documented by Kunqian Yu of the Shanghai Institute of Materia Medica and colleagues (G. Qiu et al., J. Phys. Chem. B 114, 8487-8493; 2010 – paper here). Their MD and quantum molecular mechanics calculations indicate that AMT binds in the pH-gated proton channel M2, as indeed it was designed to do. Here the drug disrupts a water wire that allows protons to cross the pore, and thereby inhibits its function. But AMT can occupy different positions in the channel, and in the resistant mutant SN13 it binds at a site that does not ‘snip’ the water wire: protons can still get through.

In photosystem II, water acts as a ligand, which is oxidized by a Mn4Ca cluster. It’s not been clear exactly where this water is bound, and that is what Robert Stranger and colleagues at ANU set out to establish using density functional calculations (S. Petrie et al., Angew. Chem. Int. Ed. 49, 4233-4236; 2010 – paper here). They find six waters bound close to the Mn cluster through the catalytic cycle, of which the two substrate waters fit in a cleft between two Mn atoms and the Ca.

The thermodynamics and kinetics of water confined between hydrophobic plates is investigated using MD with a simple monoatomic water model by Limei Xu and Valeria Molinero (J. Phys. Chem. B 114, 7320-7328; 2010 – paper here). They consider the conditions under which drying is induced, and look at the marginal situation in which there are rapid fluctuations between a wet and dry state. One obviously has to ask to what extent the quantitative conclusions here would apply to more sophisticated water potentials, but I’m also left to wonder whether the authors have really made proper contact with the vast earlier literature on liquid-vapour phase transitions in confined systems.

Shiang-Tai Lin at the National Taiwan University and colleagues present a method for calculating the entropy and energy of molecular liquids from the trajectory of MD simulations, which they apply to water using various potentials (S.-T. Lin et al., J. Phys. Chem. B 10.1021/jp103120q – paper here). They show that the technique has rapid convergence: these thermodynamic quantities can be computed from just 10 ps of simulation time.

Evan Williams and colleagues at Berkeley have used infrared photodissociation spectroscopy to investigate water-structuring effects of sulphate ions hydrated within clusters of up to 80 water molecules at 130 K (J. T. O’Brien et al., JACS 10.1021/ja1024113 – paper here). They present these results within the context of ‘structure-making and –breaking’ in the Hofmeister series, although naturally it is an open question to what extent the structures seen here reflect those in bulk solution at ambient temperatures. They say they see the spectral signature of bulk-like water – or more precisely, of free OH groups at the cluster surfaces analogous to those at the bulk surface – for clusters with more than about 43 water molecules, equivalent to the third solvation shell. The authors say that in fact their results imply that, although a sulphate ion ‘patterns’ water molecules ‘to a distance much farther than the first solvation shell’, this does not alter the number and strength of the hydrogen bonds beyond the first shell. But it is not really clear what the consequences for Hofmeister effects are, beyond the suggestion by Williams et al. that experiments that probe only rotational dynamics may miss some of the more subtle ‘patterning’ (presumably ordering) effects evident in this spectroscopic study.

Andrei Sommer and his colleagues have extended their previous investigations of the anticancer effects of red light and green tea (thought to be operating via photo-induced changes in the ordering of interfacial water – see here) (A. P. Sommer et al., Photomed. Laser Surg. 28, 429-430; 2010 – paper here). They find that the two things administered together retard the growth of HeLa cells. The mechanism remains speculative.

MD simulations with explicit water are computationally intensive, for which reason Piotr Setny and Martin Zacharias at the TU Munich have developed a computationally efficient way to model hydration (J. Phys. Chem. B 10.1021/jp102462s – paper here). It is a lattice cellular automaton that calculates solute-solvent and solvent-solvent interaction energies using a mean-field approach, which can calculate whether a particular grid cell at the solute surface is hydrated. It performs well in terms of predicting hydration energies for drug molecules, as well as locating buried water molecules in cavities.

Water molecules passing through carbon nanotubes can be pulled by methane molecules across the potential barriers created by tapering junctions where two tubes of different radii are joined, according to simulations by H. Li at Shandong University in Jinan, China, and colleagues (H. Q. Yu et al., J. Chem. Phys. B 10.1021/jp102810j – paper here). The ‘dragging’ effect is mediated by van der Waals interactions, they say.

13 comments:

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