Ion Specific Protein Assembly and Hydrophobic Surface Forces

Abstract

Large anions are attracted to hydrophobic surfaces while smaller, well solvated ions are repelled. Using a combination of explicit solvent and continuum model simulations we show that this leads to significant ion-specific protein-protein interactions due to hydrophobic patches on the protein surfaces. In solutions of NaI and NaCl we calculate the potentials of mean force and find that the resulting second virial coefficients for lysozyme correspond well with experiment. We argue that ionic interactions with nonpolar surface groups may play an important role for biomolecular assembly and Hofmeister-type effects.Molecular dynamics (MD) simulations [1][2][3][4][5] have shown that large anions are attracted to hydrophobic interfaces while smaller anions are repelled. These findings are supported by a number of experimental studies [6 -11]. Measurements on bulk electrolytes also indicate that nonpolar surfaces interact more strongly with ions of larger size. For example, excess chemical potential differences, ex for salts with identical cations measure the change in free energy associated with anion exchange. Exchanging iodide with chloride in the presence of a common cation M, one obtains ex I!Cl ln MCl = MI , where are the mean activity coefficients and is the inverse thermal energy. Experimental measurements for this quantity are shown in Fig. 1, for a series of increasingly hydrophobic alkyl ammonium cations. The results indicate that chloride is the favored anion for the small ammonium ion ( ex < 0) while increasing the alkyl chain length of the cation causes a shift in preference towards iodide ( ex > 0).Similar ion-specific surface effects may also play an important role in protein solutions. While the interface of water soluble, globular proteins are usually polar, solvent exposed patches of hydrophobic surface groups do indeed occur [12]. In recent simulation work [5] we showed that iodide ions show a preference for hydrophobic regions of a simple, nonspecific, protein model. This being the case, it is then likely that ion adsorption at hydrophobic surfaces will also affect the important phenomenon of protein aggregation. Tellingly, light scattering experiments [13] and crystallization studies [14] show that the self-association of the lysozyme protein is assisted by large anions such as iodide and thiocyanate, while the influence of chloride is less pronounced. Despite this evidence, specific ion binding to nonpolar surface groups has not yet been explicitly included in any theoretical studies on protein aggregation. In previous work [15][16][17] ion-specific association has instead been attributed to attractive dispersion interactions between ions and charged macrospheres. However, simulations using explicit solvent models of ions at surfaces [4,5,18] suggest that surface modified ion solvation plays a major role in the ion-surface interaction and that, surprisingly, the water mediated dispersion component of the interaction may even be repulsive [4]. The aim of the work, reported in this Letter, is to pro...

The inverse and direct Hofmeister series for lysozyme

“…The presence of electrolyte ions in the solution, however, changes this situation. When chaotropic anions associate with positively charged sites on the protein surface, the effective surface charge on the macromolecule will be reduced (31)(32)(33). This in turn diminishes the surface potential of the protein/water interface causing the cloud-point temperature to rise.…”

Adsorption of thiocyanate ions to the dodecanol/water interface characterized by UV second harmonic generation

“…Weakly hydrated ions have been shown to adsorb to air/water and hydrophobic/water interfaces by both experiment (10,11,39,40) and theory (14,16,41), presumably due to hydrophobic effects, resulting in minimal disruption of the strong hydrogen bonding interactions of water. However, since the structure of the surfactant is unchanged by the presence of ions in similar systems (9,29) and the dodecanol layer is part of the hydrogen bond network at the interface, the energetic preference of ions for the interface due to hydrophobic exclusion may be less than at the air/water interface.…”

“…The prevailing explanation for the Hofmeister series invokes specific ion interactions at the macromolecule/water interface (5,9,(12)(13)(14)(15)(16)(17)(18)(19). To experimentally assess more complex issues, such as protein solubility and enzyme inhibition the interactions of ions with specific and relevant chemical moieties must be understood.…”

“…Collins has proposed the ''law of matching water affinities'' to explain Hofmeister effects, which utilizes ion hydration strength to explain ionspecific interactions (12). Jungwirth et al have recently performed a number of simulations investigating the relation between the Hofmeister series and specific-ion interactions with various model and chemical interfaces (13)(14)(15)(16)(17)(18)(19). In one of these studies, ions at opposite ends of the Hofmeister anion series, fluoride and iodide, exhibit two different mechanisms of adsorption to a model macromolecule (16).…”

Experimental demonstration of a Hadamard gate for coherent state qubits

“…Although these states are only approximately orthogonal ( α| − α = 0), resource efficient and fault tolerant quantum gates can be implemented: For a large coherent amplitude, that is α > 2, deterministic gates can in principle be realized although the experimental implementation is very challenging [5]. On the other hand, by employing a simpler physical implementation, non-deterministic gates can be realized for any value of α, and for α > 1.2, the scheme was theoretically shown to be fault-tolerant and resource efficient [6].An even simpler implementation of a universal set of non-deterministic quantum gates was recently suggested by Marek and Fiurášek [7]. They proposed the physical realization of a single mode and a two-mode phase gate as well as the Hadamard gate.…”