An understanding of molecular interactions is essential for insight into biological systems at the molecular scale. Among the various components of molecular interactions, electrostatics are of special importance because of their long-range nature and their influence on polar or charged molecules, including water, aqueous ions, proteins, nucleic acids, carbohydrates, and membrane lipids. In particular, robust models of electrostatic interactions are essential for understanding the solvation properties of biomolecules and the effects of solvation upon biomolecular folding, binding, enzyme catalysis, and dynamics. Electrostatics, therefore, are of central importance to understanding biomolecular structure and modeling interactions within and among biological molecules. This review discusses the solvation of biomolecules with a computational biophysics view towards describing the phenomenon. While our main focus lies on the computational aspect of the models, we provide an overview of the basic elements of biomolecular solvation (e.g., solvent structure, polarization, ion binding, and nonpolar behavior) in order to provide a background to understand the different types of solvation models.

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The adsorption behavior of hard and soft proteins under the effect of an external electric field was investigated by a combination of spectroscopic ellipsometry and molecular dynamics (MD) simulations. Optically transparent carbon electrodes (OTCE) were used as conductive, sorbent substrates. Lysozyme (LSZ) and ribonuclease A (RNase A) were selected as representative hard proteins whereas myoglobin (Mb), α-lactalbumin (α-LAC), bovine serum albumin (BSA), glucose oxidase (GOx), and immunoglobulin G (IgG) were selected to represent soft proteins. In line with recent publications from our group, the experimental results revealed that while the adsorption of all investigated proteins can be enhanced by the potential applied to the electrode, the effect is more pronounced for hard proteins. In contrast with the incomplete monolayers formed at open-circuit potential, the application of +800mV to the sorbent surface induced the formation of multiple layers of protein. These results also suggest that this effect can be related to the intrinsic polarizability of the protein (induction of dipoles), the resulting surface accessible solvent area (SASA), and structural rearrangements induced upon the incorporation on the protein layer. The described experiments are critical to understand the relationship between the structure of proteins and their tendency to form (under electric stimulation) layers with thicknesses that greatly surpass those obtained at open-circuit conditions.

In this article, we present a classical density functional theory for electrical double layers of spherical macroions that extends the capabilities of conventional approaches by accounting for electrostatic ion correlations, size asymmetry, and excluded volume effects. The approach is based on a recent approximation introduced by Hansen-Goos and Roth for the hard sphere excess free energy of inhomogeneous fluids [J. Chem. Phys. 124, 154506 (2006); J. Phys.: Condens. Matter 18, 8413 (2006)]. It accounts for the proper and efficient description of the effects of ionic asymmetry and solvent excluded volume, especially at high ion concentrations and size asymmetry ratios including those observed in experimental studies. Additionally, we utilize a leading functional Taylor expansion approximation of the ion density profiles. In addition, we use the mean spherical approximation for multi-component charged hard sphere fluids to account for the electrostatic ion correlation effects. These approximations are implemented in our theoretical formulation into a suitable decomposition of the excess free energy which plays a key role in capturing the complex interplay between charge correlations and excluded volume effects. We perform Monte Carlo simulations in various scenarios to validate the proposed approach, obtaining a good compromise between accuracy and computational cost. We use the proposed computational approach to study the effects of ion size, ion size asymmetry, and solvent excluded volume on the ion profiles, integrated charge, mean electrostatic potential, and ionic coordination number around spherical macroions in various electrolyte mixtures. Our results show that both solvent hard sphere diameter and density play a dominant role in the distribution of ions around spherical macroions, mainly for experimental water molarity and size values where the counterion distribution is characterized by a tight binding to the macroion, similar to that predicted by the Stern model. © 2014 AIP Publishing LLC. [http://dx

An accurate and efficient characterization of the polyelectrolyte properties for cytoskeleton filaments are key to the molecular understanding of electrical signal propagation, bundle and network formation, as well as their potential nanotechnological applications. In this article, we introduce an innovative multi-scale approach able to account for the atomistic details of a protein molecular structure, its biological environment, and their impact on electrical impulses propagating along wild type Actin filaments. The formulation includes non trivial contributions to the ionic electrical conductivity and capacitance coming from the diffuse part of the electrical double layer of G-actins. We utilize this monomer characterization in a nonlinear inhomogeneous transmission line prototype model to account for the monomer-monomer interactions, dissipation and damping perturbations along the filament length. A novel, simple, accurate, approximate analytic expression has been obtained for the transmission line model. Our results reveal the propagation of electrical signal impulses in the form of solitons for the range of voltage stimulus and electrolyte solutions typically present for intracellular and in-vitro conditions. The approach predicts a lower electrical conductivity with higher linear capacitance and nonlinear accumulation of charge for intracellular conditions. Our results show a significant influence of the voltage input on the electrical impulse shape, attenuation and kern propagation velocity. The filament is able to sustain the soliton propagation at almost constant kern velocity for the in-vitro condition, whereas the intracellular condition displays a remarkable deceleration. Additionally, the solitons are narrower and travel faster at higher voltage input. As a unique feature, this multi-scale theory is able to account for molecular structure conformation (mutation) and biological environment (protonations/deprotonations) changes often present in pathological conditions. It is also applicable to other highly charged rod-like polyelectrolytes with relevance in biomedicine and biophysics.