Ana Vila Verde

Investigating the specificity of peptide adsorption on gold using molecular dynamics simulations

We report all-atom molecular dynamics simulations following adsorption of gold-binding and non-gold-binding peptides on gold surfaces modeled with dispersive interactions. We examine the dependence of adsorption on both identity of the amino acids and mobility of the peptides. Within the limitations of the approach, results indicate that when the peptides are solvated, adsorption requires both configurational changes and local flexibility of individual amino acids. This is achieved when peptides consist mostly of random coils or when their secondary structural motifs (helices, sheets) are short and connected by flexible hinges. In the absence of solvent, only affinity for the surface is required: mobility is not important. In combination, these results suggest the barrier to adsorption presented by displacement of water molecules requires conformational sampling enabled through mobility.

Adsorption of homopolypeptides on gold investigated using atomistic molecular dynamics.

We investigate the role of dynamics on adsorption of peptides to gold surfaces using all-atom molecular dynamics simulations in explicit solvent. We choose six homopolypeptides [Ala(10), Ser(10), Thr(10), Arg(10), Lys(10), and Gln(10)], for which experimental surface coverages are not correlated with amino acid level affinities for gold, with the idea that dynamic properties may also play a role. To assess dynamics we determine both conformational movement and flexibility of the peptide within a given conformation. Low conformational movement indicates stability of a given conformation and leads to less adsorption than homopolypeptides with faster conformational movement. Likewise, low flexibility within a given conformation also leads to less adsorption. Neither amino acid affinities nor dynamic considerations alone predict surface coverage; rather both quantities must be considered in peptide adsorption to gold surfaces.

Disaccharide Topology Induces Slowdown in Local Water Dynamics

Molecular level insight into water structure and structural dynamics near proteins, lipids, and nucleic acids is critical to the quantitative understanding of many biophysical processes. Unfortunately, understanding hydration and hydration dynamics around such large molecules is challenging because of the necessity of deconvoluting the effects of topography and chemical heterogeneity. Here we study, via classical all-atom simulation, the water structure and structural dynamics around two biologically relevant solutes large enough to have significant chemical and topological heterogeneity but small enough to be computationally tractable: the disaccharides kojibiose and trehalose. We find both molecules to be strongly amphiphilic (as quantified from normalized local density fluctuations) and to induce nonuniform local slowdown in water translational and rotational motions. Detailed analysis of the rotational slowdown shows that, while the rotational mechanism is similar to that previously identified in other aqueous systems by Laage, Hynes, and coworkers, two novel characteristics are observed: broadening of the transition state during hydrogen bond exchange (water rotation) and a subpopulation of water for which rotation is slowed because of hindered access of the new accepting water molecule to the transition state. Both characteristics are expected to be generic features of water rotation around larger biomolecules and, taken together, emphasize the difficulty in transferring insight into water rotation around small molecules to much larger amphiphilic solutes.

Simulation study of micelle formation by bile salts

We report coarse-grained, implicit-solvent simulations of aqueous solutions of bile salts. The parameters in our model were optimized to reproduce some of the experimentally known behavior of dihydroxy bile salts at “physiological” temperature and counterion concentration. We find that micelle formation in dihydroxy and trihydroxy bile salts is only weakly cooperative in the sense that there is barely a free energy barrier that stabilizes these micelles against disassembly. Bile molecules are found to pack in many different orientations in pure bile micelles. Both features may be physiologically relevant: the ability to pack in different orientations may be necessary to form mixed micelles with nutrients of a wide range of molecular lengths and shapes, and the reduced micelle stability may facilitate nutrient release once the mixed micelles reach the intestinal wall.

Temperature-sensitive colloidal phase behavior induced by critical Casimir forces

We report Monte Carlo simulations of phase behavior of colloidal suspensions with near-critical binary solvents using effective pair potentials from experiments. At off-critical solvent composition, the calculated phase diagram agrees well with measurements of the experimental system, indicating that many-body effects are limited. Close to the critical composition, however, agreement between experiment and simulation becomes poorer, signaling the increased importance of many-body effects. Both at and off the critical solvent concentration, the colloidal phase diagram is qualitatively similar to those of molecular systems and obeys the principle of corresponding states with one striking difference: it occurs in a narrow temperature interval of <1 °C below the solvent phase separation temperature.

The Free OD at the Air/D2O Interface is Structurally and Dynamically Heterogeneous

Air/water interfaces are both ubiquitous in the environment and technology and a useful model for hydrophobic solvation more generally. Previous experimental and computational studies have highlighted that molecular level markers of such an extended hydrophobic surface are broken hydrogen bonds and, as a result, OH groups that are not hydrogen bond donors: free OH. Understanding both the time-averaged structure and structural dynamics of these free OH thus plays a critical role in developing a quantitative, molecular level understanding of hydrophobic solvation. Here we show, by combining polarization-dependent vibrational sum frequency (VSF) spectroscopy and molecular dynamics simulation, that the free OD of D2O at the air/D2O interface is structurally and dynamically heterogeneous: that longer lived free OD groups tend to point closer to the surface normal, have a narrower orientational distribution, and are closer to the vapor phase. Knowledge of this structural heterogeneity should help link existing descriptions of hydrophobic solvation that focus either on the termination of the bulk hydrogen bond network or local density fluctuations. In addition the results of this study clarify that schemes to increase signal-to-noise ratios in VSF measurements by delaying the visible pulse relative to the infrared should be used only with independent constraints on the systems structural dynamics.

Is the Solution Activity Derivative Sufficient to Parametrize Ion–Ion Interactions? Ions for TIP5P Water

Biomolecular processes involve hydrated ions, and thus molecular simulations of such processes require accurate force-field parameters for these ions. In the best force-fields, both ion-water and anion-cation interactions are explicitly parametrized. First, the ion Lennard-Jones parameters are optimized to reproduce, for example, single ion solvation free energies; then ion-pair interactions are adjusted to match experimental activity or activity derivatives. Here, we apply this approach to derive optimized parameters for concentrated NaCl, KCl, MgCl2, and CaCl2 salt solutions, to be used with the TIP5P water model. These parameters are of interest because of a number of desirable properties of the TIP5P water model, especially for the simulation of carbohydrates. The results show, that this state of the art approach is insufficient, because the activity derivative often reaches a plateau near the target experimental value, for a wide range of parameter values. The plateau emerges from the interconversion between different types of ion pairs, so parameters leading to equally good agreement with the target solution activity or activity derivative yield very different solution structures. To resolve this indetermination, a second target property, such as the experimentally determined ion-ion coordination number, is required to uniquely determine anion-cation interactions. Simulations show that combining activity derivatives and coordination number as experimental target properties to parametrize ion-ion interactions, is a powerful method for reliable ion-water force field parametrization, and gives insight into the concentration of contact or solvent shared ion pairs in a wide range of salt concentrations. For the alkali and halide ions Li+, Rb+, Cs+, F-, Br-, and I-, we present ion-water parameters appropriate at infinite dilution only.