How interface geometry dictates water's thermodynamic signature in hydrophobic association

As a common view the hydrophobic association between molecular-scale binding partners is supposed to be dominantly driven by entropy. Recent calorimetric experiments and computer simulations heavily challenge this established paradigm by reporting that water's thermodynamic signature in the binding of small hydrophobic ligands to similar-sized apolar pockets is enthalpy-driven. Here we show with purely geometric considerations that this controversy can be resolved if the antagonistic effects of concave and convex bending on water interface thermodynamics are properly taken into account. A key prediction of this continuum view is that for fully complementary binding of the convex ligand to the concave counterpart, water shows a thermodynamic signature very similar to planar (large-scale) hydrophobic association, that is, enthalpy-dominated, and hardly depends on the particular pocket/ligand geometry. A detailed comparison to recent simulation data qualitatively supports the validity of our perspective down to subnanometer scales. Our findings have important implications for the interpretation of thermodynamic signatures found in molecular recognition and association processes. Furthermore, traditional implicit solvent models may benefit from our view with respect to their ability to predict binding free energies and entropies.Comment: accepted for publication in J. Stat. Phys., special issue on water&associated liquid

Equilibrium structure and fluctuations of suspensions of colloidal dumbbells

We investigate the structure and equilibrium linear-response dynamics of suspensions of hard colloidal dumbbells using Brownian Dynamics computer simulations. The focus lies on the dense fluid and plastic crystal states of the colloids with investigated aspect (elongation-to-diameter) ratios varying from the hard sphere limit up to 0.39, which is roughly the stability limit of the plastic crystal phase. We find expected structural changes with larger elongation with respect to the hard sphere reference case and very localized orientational correlations, typically just involving next-neighbor couplings. These relatively weak correlations are also reflected in only minor effects on the translational and rotational diffusion coefficients for most of the investigated elongations. However, the linear response shear viscosity exhibits a dramatic increase at high packing fractions ($\phi\gtrsim 0.5$) beyond a critical anisotropy factor of about $L^* \simeq 0.15$ which is surprising in view of the relatively weak changes found before on the level of colloidal self-dynamics. We suspect that even for the small investigated anisotropies, newly occurring, collective rotational-translational couplings must be made responsible for the slow time scales appearing in the plastic crystal.Comment: Molecular Physics 201

Dynamic density functional theory of protein adsorption on polymer-coated nanoparticles

We present a theoretical model for the description of the adsorption kinetics of globular proteins onto charged core-shell microgel particles based on Dynamic Density Functional Theory (DDFT). This model builds on a previous description of protein adsorption thermodynamics [Yigit \textit{et al}, Langmuir 28 (2012)], shown to well interpret the available calorimetric experimental data of binding isotherms. In practice, a spatially-dependent free-energy functional including the same physical interactions is built, and used to study the kinetics via a generalised diffusion equation. To test this model, we apply it to the case study of Lysozyme adsorption on PNIPAM coated nanoparticles, and show that the dynamics obtained within DDFT is consistent with that extrapolated from experiments. We also perform a systematic study of the effect of various parameters in our model, and investigate the loading dynamics as a function of proteins' valence and hydrophobic adsorption energy, as well as their concentration and that of the nanoparticles. Although we concentrated here on the case of adsorption for a single protein type, the model's generality allows to study multi-component system, providing a reliable instrument for future studies of competitive and cooperative adsorption effects often encountered in protein adsorption experiments.Comment: Submitted to Soft Matte

Curvature Dependence of Hydrophobic Hydration Dynamics

We investigate the curvature-dependence of water dynamics in the vicinity of hydrophobic spherical solutes using molecular dynamics simulations. For both, the lateral and perpendicular diffusivity as well as for H-bond kinetics of water in the first hydration shell, we find a non-monotonic solute-size dependence, exhibiting extrema close to the well-known structural crossover length scale for hydrophobic hydration. Additionally, we find an apparently anomalous diffusion for water moving parallel to the surface of small solutes, which, however, can be explained by topology effects. The intimate connection between solute curvature, water structure and dynamics has implications for our understanding of hydration dynamics at heterogeneous biomolecular surfaces.Comment: 10 pages, 9 figure

Solvent fluctuations induce non-Markovian kinetics in hydrophobic pocket-ligand binding

We investigate the impact of water fluctuations on the key-lock association kinetics of a hydrophobic ligand (key) binding to a hydrophobic pocket (lock) by means of a minimalistic stochastic model system. It describes the collective hydration behavior of the pocket by bimodal fluctuations of a water-pocket interface that dynamically couples to the diffusive motion of the approaching ligand via the hydrophobic interaction. This leads to a set of overdamped Langevin equations in 2D-coordinate-space, that is Markovian in each dimension. Numerical simulations demonstrate locally increased friction of the ligand, decelerated binding kinetics, and local non-Markovian (memory) effects in the ligand's reaction coordinate as found previously in explicit-water molecular dynamics studies of model hydrophobic pocket-ligand binding [1,2]. Our minimalistic model elucidates the origin of effectively enhanced friction in the process that can be traced back to long-time decays in the force-autocorrelation function induced by the effective, spatially fluctuating pocket-ligand interaction. Furthermore, we construct a generalized 1D-Langevin description including a spatially local memory function that enables further interpretation and a semi-analytical quantification of the results of the coupled 2D-system