No abstract

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.ion-protein interaction ͉ molecular dynamics ͉ cell environment ͉ protein function ͉ Hofmeister series S odium and potassium represent the two most abundant monovalent cations in living organisms. Despite the fact that they possess the same charge and differ only in size [Na ϩ having a smaller ionic radius but a larger hydrated radius than K ϩ (1)], sodium versus potassium ion specificity plays a crucial role in many biochemical processes. More than 100 years ago, Hofmeister discovered that Na ϩ destabilizes (''salts out'') hens' egg white protein more efficiently than K ϩ does (2), analogous behavior being later shown also for other proteins (3). In a similar way, sodium was found to be significantly more efficient than potassium, e.g., in enhancing polymerization of rat brain tubulin (4). 23 Na NMR studies also were used to characterize cation-binding sites in proteins (5). The vital biological relevance of the difference between Na ϩ and K ϩ is exemplified by the low intracellular and high extracellular sodium͞potassium ratio maintained in living cells by ion pumps at a considerable energy cost (6). The principal goal of this article is to quantify and rationalize the different affinities of sodium and potassium to protein surfaces by means of molecular dynamics (MD) simulations, quantum chemistry calculations, and conductivity measurements for a series of proteins and protein fragments in aqueous solutions. Our effort, which is aimed at understanding the generic, thermodynamic Na ϩ ͞K ϩ ion specificity at protein surfaces, is thus complementary to recent computational studies of ion selectivity during active transport across ...

Clathrate hydrates (CHs) are inclusion compounds in which "tetrahedrally" bonded H(2)O forms a crystalline host lattice composed of a periodic array of cages. The structure is stabilized by guest particles which occupy the cages and interact with cage walls via van der Waals interactions. A host of atoms or small molecules can act as guests; here the focus is on guests that are capable of strong to intermediate H-bonding to water (small ethers, H(2)S, etc.) but nevertheless "choose" this hydrate crystal form in which H-bonding is absent from the equilibrium crystal structure. These CHs can form by exposure of ice to guest molecules at temperatures as low as 100-150 K, at the (low) guest saturation pressure. This is in contrast to the "normal" CHs whose formation typically requires temperatures well above 200 K and at least moderate pressures. The experimental part of this study addresses formation kinetics of CHs with H-bonding guests, as well as transformation kinetics between different CH forms, studied by CH infrared spectroscopy. The accompanying computational study suggests that the unique properties of this family of CHs are due to exceptional richness of the host lattice in point defects, caused by defect stabilization by H-bonding of water to the guests.

Relative interaction strengths between cations (X = Li (+), Na (+), K (+), NH 4 (+)) and anionic carboxylate groups of acetate and glycine in aqueous solution are determined. These model systems mimic ion pairing of biologically relevant cations with negatively charged groups at protein surfaces. With oxygen 1s X-ray absorption spectroscopy, we can distinguish between spectral contributions from H 2O and carboxylate, which allows us to probe the electronic structure changes of the atomic site of the carboxylate group being closest to the countercation. From the intensity variations of the COO (-) aq O 1s X-ray absorption peak, which quantitatively correlate with the change in the local partial density of states from the carboxylic site, interactions are found to decrease in the sequence Na (+) > Li (+) > K (+) > NH 4 (+). This ordering, as well as the observed bidental nature of the -COO (-) aq and X (+) aq interaction, is supported by combined ab initio and molecular dynamics calculations.