Luboš Vrbka

Quantification and rationalization of the higher affinity of sodium over potassium to protein surfaces

For a series of different proteins, including a structural protein, enzyme, inhibitor, protein marker, and a charge-transfer system, we have quantified the higher affinity of Na+ over K+ to the protein surface by means of molecular dynamics simulations and conductivity measurements. Both approaches show that sodium binds at least twice as strongly to the protein surface than potassium does with this effect being present in all proteins under study. Different parts of the protein exterior are responsible to a varying degree for the higher surface affinity of sodium, with the charged carboxylic groups of aspartate and glutamate playing the most important role. Therefore, local ion pairing is the key to the surface preference of sodium over potassium, which is further demonstrated and quantified by simulations of glutamate and aspartate in the form of isolated amino acids as well as short oligopeptides. As a matter of fact, the effect is already present at the level of preferential pairing of the smallest carboxylate anions, formate or acetate, with Na+ versus K+, as shown by molecular dynamics and ab initio quantum chemical calculations. By quantifying and rationalizing the higher preference of sodium over potassium to protein surfaces, the present study opens a way to molecular understanding of many ion-specific (Hofmeister) phenomena involving protein interactions in salt solutions.

Specific ion binding to nonpolar surface patches of proteins

Employing detailed atomistic modeling we study the mechanisms behind ion binding to proteins and other biomolecules and conclude that (1) small, hard ions bind via direct ion pairing to charged surface groups and (2) large, soft ions bind to nonpolar groups via a solvent assisted attraction. Our predictions are in qualitative agreement with bulk solution data and may provide an important clue for the basic understanding of ion-specific effects in biological systems.

Specificity of Ion−Protein Interactions: Complementary and Competitive Effects of Tetrapropylammonium, Guanidinium, Sulfate, and Chloride Ions

The interactions of ions with a model peptide (a single melittin alpha-helix) in solutions of tetrapropylammonium sulfate or guanidinium chloride were examined by molecular dynamics simulations. The tetrapropylammonium cation shares the geometrical property of essentially flat faces with the previously examined guanidinium cation, and it was found that that this geometry leads to a strong preference for tetrapropylammonium to interact in a similar stacking-type fashion with flat nonpolar groups such as the indole side chain of tryptophan. In contrast to guanidinium, however, tetrapropylammonium does not exhibit strong ion pairing or clustering with sulfate counterions in the solution. Sulfate was found to interact almost exclusively and strongly with the cationic groups of the peptide, such that, already in a 0.1 m solution of tetrapropylammonium sulfate, the 6+ charge of the peptide is effectively locally neutralized. In combination with previous simulations, neutron scattering studies, and experiments on the conformational stability of model peptides, the present results suggest that the Hofmeister series can be explained in higher detail by splitting ions according to the effect they have on hydrogen bonding, salt bridges, and hydrophobic interactions in the protein and how these effects are altered by the counterion.

Carbon monoxide adsorption on low-silica zeolites-from single to dual and to multiple cation sites

Infrared spectra of CO adsorbed on the Al-rich Na-A zeolite were analysed by using a combined theoretical and experimental approach, showing that such spectra cannot be interpreted by assigning each IR band to CO interacting with a specific type of single cation site. This concept, which usually works well for high-silica zeolites, should not be uncritically extended to Al-rich zeolites that are crowded with cations in configurations which lead to preferential formation of CO adsorption complexes involving more than one cation site.

Ion-specific thermodynamics of multicomponent electrolytes: A hybrid HNC/MD approach

Using effective infinite dilution ion-ion interaction potentials derived from explicit-water molecular dynamics (MD) computer simulations in the hypernetted-chain (HNC) integral equation theory we calculate the liquid structure and thermodynamic properties, namely, the activity and osmotic coefficients of various multicomponent aqueous electrolyte mixtures. The electrolyte structure expressed by the ion-ion radial distribution functions is for most ions in excellent agreement with MD and implicit solvent Monte Carlo (MC) simulation results. Calculated thermodynamic properties are also represented consistently among these three methods. Our versatile HNC/MD hybrid method allows for a quick prediction of the thermodynamics of multicomponent electrolyte solutions for a wide range of concentrations and an efficient assessment of the validity of the employed MD force-fields with possible implications in the development of thermodynamically consistent parameter sets.

Ion specific effects of sodium and potassium on the catalytic activity of HIV-1 protease

The behavior of HIV-1 protease in aqueous NaCl and KCl solutions is investigated by kinetic measurements and molecular dynamics simulations. Experiments show cation-specific effects on the enzymatic activity. The initial velocity of peptide substrate hydrolysis increases with salt concentration more dramatically in potassium than in sodium chloride solutions. Furthermore, significantly higher catalytic efficiencies (k(cat)/K(M)) are observed in the presence of K+ compared to Na+ at comparable salt concentrations. Molecular dynamics simulations provide insight into this ion-specific behavior. Sodium is attracted more strongly than potassium to the protein surface primarily due to stronger interactions with carboxylate side chain groups of aspartates and glutamates. These effects are of particular importance for acidic amino acid residues at or near the active site of the enzyme, including a pair of aspartates at the entrance to the reaction cavity. We infer that the presence of more Na+ than K+ at the active site leads to a lower increase in enzymatic activity with increasing salt concentration in the presence of Na+, likely due to the ability of the alkali cations at the active site to lower the efficiency of substrate binding.

Interaction of acetonitrile with Na-zeolites: adsorption modes and vibrational dynamics in the zeolite channels and cavities

The interaction of acetonitrile with the extra-framework Na(+) cations in zeolites, namely Na-LTA and Na-FER, was investigated. The relative stabilities of possible types of adsorption complexes were calculated at the periodic DFT level. Individual effects on the complex stability and on the vibrational dynamics of adsorbed acetonitrile were qualitatively analysed on various cluster models. The acetonitrile primarily interacts with the Na(+) cation (via the N end), and the complex stability is modulated by the interaction of the methyl group with the framework oxygen atoms, which has a partial hydrogen-bond character. In line with the results of recent analyses of CO interactions with metal-exchanged zeolites [D. Nachtigallová, O. Bludský, C. O. Areán, R. Bulanek and P. Nachtigall, Phys. Chem. Chem. Phys., 2006, 8, 4849], two types of effects should be taken into consideration for acetonitrile complexes in Na-zeolites: (i) the effects from the bottom, reflecting the accessibility and coordination of the primary metal cation, to which the acetonitrile molecule is bonded via the N atom; and (ii) the effects from the top, including H-bond formation (stabilising effect) or repulsion due to the secondary metal cation. The effect from the bottom results in a blue shift of nu(CN) while the effect from the top (H-bond formation) results in a red shift in both nu(CN) and nu(CH).

Counter-Ion Effects and Interfacial Properties of Aqueous Tetrabutylammonium Halide Solutions

Aqueous solvation of tetrabutylammonium fluoride and iodide was investigated by means of molecular dynamics simulations in extended slab geometry. The varying propensities of the individual ions for the air/water interface were quantified and analyzed in terms of hydrophobic, polarization, and ion–ion interactions. While the cations behave as standard ionic surfactants, the surface behaviour of the halide counter ions strongly depends on the ionic size and polarizability—iodide is surface active, while fluoride is repelled from the interface. The counter-ion effects at different concentrations on the density and charge profiles across the aqueous slab are discussed in detail.