Long-range Electrostatic Interactions Research Articles

Transient Electrostatic Interactions between Fcp1 and Rap74 Bias the Conformational Ensemble of the Complex with Minimal Impact on Binding Affinity.

Intrinsically disordered protein (IDP) sequences often contain a high proportion of charged residues in conjunction with their high degree of hydrophilicity and solvation. For high net charge IDPs, long-range electrostatic interactions are thought to play a role in modulating the strength or kinetics of protein-protein interactions. In this work, we examined intramolecular interactions mediated by charged regions of a model IDP, the C-terminal tail of the phosphatase Fcp1. Specifically, this work focuses on intermolecular interactions between acidic and basic patches in the primary structure of Fcp1 and their contributions to binding its predominantly basic partner, the winged helix domain of Rap74. We observe both intramolecular and intermolecular interactions through paramagnetic relaxation enhancement (PRE) consistent with oppositely charged regions associating with one another, both in unbound Fcp1 and in the Fcp1-Rap74 complex. Formation of this complex is strongly driven by hydrophobic interactions in the minimal binding motif. Here, we test the hypothesis that charged residues in Fcp1 that flank the binding helix also contribute to the strength of binding. Charge inversion mutations in Fcp1 generally support this hypothesis, while PRE data suggest substitution of observed transient interactions in the unbound ensemble for similarly transient interactions with Rap74 in the complex.

Theory of plasmonic edge states in chiral bilayer systems

We analytically describe the plasmonic edge modes for an interface that involves the twisted bilayer graphene (TBG) or other similar Moire van der Waals heterostructure. For this purpose, we employ a spatially homogeneous, isotropic and frequency-dependent tensor conductivity which in principle accounts for electronic and electrostatic interlayer couplings. We predict that the edge mode dispersion relation explicitly depends on the chiral response even in the nonretarded limit, in contrast to the collective bulk plasmonic excitations in the TBG. We obtain a universal function for the dispersion of the optical edge plasmon in the paramagnetic regime. This implies a correspondence of the chiral-TBG optical plasmon to a magnetoplasmon of a single sheet, and chirality is interpreted as an effective magnetic field. The chirality also opens up the possibility of nearly undamped acoustic modes in the paramagnetic regime. Our results may guide future near-field nanoscopy for van der Waals heterostructures. In our analysis, we retain the long-range electrostatic interaction, and apply the Wiener-Hopf method to a system of integral equations for the scalar potentials of the two layers.

Long-Range Electrostatic Colloidal Interactions and Specific Ion Effects in Deep Eutectic Solvents.

While the traditional consensus dictates that high ion concentrations lead to negligible long-range electrostatic interactions, we demonstrate that electrostatic correlations prevail in deep eutectic solvents where intrinsic ion concentrations often surpass 2.5 M. Here we present an investigation of intermicellar interactions in 1:2 choline chloride:glycerol and 1:2 choline bromide:glycerol using small-angle neutron scattering. Our results show that long-range electrostatic repulsions between charged colloidal particles occur in these solvents. Interestingly, micelle morphology and electrostatic interactions are modulated by specific counterion condensation at the micelle interface despite the exceedingly high concentration of the native halide from the solvent. This modulation follows the trends described by the Hofmeister series for specific ion effects. The results are rationalized in terms of predominant ion–ion correlations, which explain the reduction in the effective ionic strength of the continuum and the observed specific ion effects.

Evidence for new enantiospecific interaction force in chiral biomolecules

Evidence for new enantiospecific interaction force in chiral biomolecules

First-principles study of electron transport in ScN

We investigate the conduction-band structure and electron mobility in rocksalt ScN based on density functional theory. The first-principles band structure allows us to obtain band velocities and effective masses as a function of energy. Electron-phonon scattering is assessed by explicitly computing the $q$-dependent electron-phonon matrix elements, with the inclusion of the long-range electrostatic interaction. The influence of free-carrier screening on the electron transport is assessed using the random-phase approximation. We find a notable enhancement of electron mobility when the carrier concentration exceeds ${10}^{20}\phantom{\rule{4pt}{0ex}}{\mathrm{cm}}^{\ensuremath{-}3}$. We calculate the room-temperature electron mobility in ScN to be 587 ${\mathrm{cm}}^{2}/\mathrm{Vs}$ at low carrier concentrations. When the carrier concentration is increased, the electron mobility starts to decrease significantly around $n={10}^{19}\phantom{\rule{4pt}{0ex}}{\mathrm{cm}}^{\ensuremath{-}3}$ and drops to 240 ${\mathrm{cm}}^{2}/\mathrm{Vs}$ at $n={10}^{21}\phantom{\rule{4pt}{0ex}}{\mathrm{cm}}^{\ensuremath{-}3}$. We also explore the influence of strain in (111)- and (100)-oriented ScN films. For (111) films, we find that a 1.0% compressive epitaxial strain increases the in-plane mobility by 72 ${\mathrm{cm}}^{2}/\mathrm{Vs}$ and the out-of-plane mobility by 50 ${\mathrm{cm}}^{2}/\mathrm{Vs}$. For (100) films, a 1.0% compressive epitaxial strain increases the out-of-plane mobility by as much as 172 ${\mathrm{cm}}^{2}/\mathrm{Vs}$, but has a weak impact on the in-plane mobility. Our study sheds light on electron transport in ScN at different electron concentrations and shows how strain engineering could increase the electron mobility.

Chiral glass of charged DNA rods, cavity loops

Recently, the collective phase behaviors of charged DNA-viruses (rods) are explored in various low ionic strengths, where much slowing down relaxations are observed in equilibrium. These phases are distinguished by crossing the critical ionic strength, where the salt-dependent effective microscopic dynamics are important with non-monotonic multi-phase boundaries. This is also interested in terms of phase transition and replica symmetry breaking (RSB), realized by the divergence of relaxation time and the exponent power of correlation lengths in dynamic disorderorder transitions. RSB occurs as the result of many-body interactions of randomized orientations. Here, in this paper, one of the chiral mesophases, the X-pattern is highlighted for its long-time metastable state consisting of cavity loops bounded within the planar nematic, as a new type of a glass, noted as a chiral glass. The chiral glass is discussed in terms of the divergences for relaxations in the characteristic time as well the inverse of an optical pitch length, which are analyzed in the long-time-lapsed orientation textures via image-time correlations. The outcome highlights interesting aspects of charge effect in the ‘twist’ elasticity energy for optimizing the long-ranged repulsive electrostatic interactions among charged DNA rods.

The Permeation Mechanism of Cisplatin Through a Dioleoylphosphocholine Bilayer*.

The investigation of the intermolecular interactions between platinum-based anticancer drugs and lipid bilayers is of special relevance to unveil the mechanisms involved in different steps of the anticancer mode of action of these drugs. We have simulated the permeation of cisplatin through a model membrane composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine lipids by means of umbrella sampling classical molecular dynamics simulations. The initial physisorption of cisplatin into the polar region of the lipid membrane is controlled by long-range electrostatic interactions with the choline groups in a first step and, in a second step, by long-range electrostatic and hydrogen bond interactions with the phosphate groups. The second half of the permeation pathway, in which cisplatin diffuses through the nonpolar region of the bilayer, is characterized by the drop of the interactions with the polar heads and the rise of attractive interactions with the non-polar tails, which are dominated by van der Waals contributions. The permeation free-energy profile is explained by a complex balance between the drug/lipid interactions and the energy and entropy contributions associated with the dehydration of the drug along the permeation pathway and with the decrease and increase of the membrane ordering along the first and second half of the mechanism, respectively.

Simulations of electroosmotic flow in charged nanopores using Dissipative Particle Dynamics with Ewald summation

We present a Dissipative Particle Dynamics simulation method that allows us to study electroosmotic flows inside cylindrical nanopores with uniform surface charge. To properly treat the long-range electrostatic interactions between all the charges, we use two different approaches. In the first approach, the uniform surface charge is represented using surface point sites. The Coulomb interaction is then treated using 3d Ewald summation with an appropriate correction for the pseudo 1d geometry. In the second approach, the surface charge is treated implicitly. It produces an external potential in which all other particles move. In the case of an infinite cylinder, the electric field produced by a uniform surface charge vanishes. However, the rest of the system is no longer charge neutral. This requires an additional correction to the Ewald summation method. Since the second method does not use the explicit surface charges, it is about 40% more efficient – while producing identical electroosmotic flow and ionic charge distribution inside the pore.

Modeling aqueous multivalent polyelectrolytes systems with polyelectrolyte NRTL model

Thermodynamic modeling of aqueous polyelectrolyte systems is of great interest in many industrial applications and biological systems. Recently a Polyelectrolyte Nonrandom Two-Liquid activity coefficient model was proposed for aqueous monovalent polyelectrolyte systems. Integrating Manning’s counterion condensation theory, Pitzer-Debye-Hückel theory, and electrolyte Nonrandom Two-Liquid theory, the model accounts for the solution nonideality derived from long-range electrostatic polyion-ion and ion-ion interactions as well as short-range van der Waals molecule–molecule, molecule-ion, and ion-ion interactions. This work extends the model for aqueous multivalent polyelectrolyte systems and shows satisfactory agreement between the model results and the available literature data on thermodynamic properties of varieties of multivalent polyelectrolyte systems.

Negative catalysis / non-Bell-Evans-Polanyi reactivity by metalloenzymes: Examples from mononuclear heme and non-heme iron oxygenases

There are many examples in bioinorganic chemistry, where metalloenzymes produce different reaction products than analogous biomimetic model complexes despite them having the same transition metal and first-coordination sphere environment. As a result, a lot of research has been devoted to the understanding of the effect of the first- and second coordination sphere of catalytic reaction centers. Thermodynamically, catalysis should follow the Bell-Evans-Polanyi principle, where the product with the largest driving force gives the lowest reaction barrier and consequently highest reaction rate and dominant reaction products. However, there are many examples in the literature, where the dominant products of an enzymatic reaction do not correspond to the reaction process with the largest exothermicity. In general, catalysis that follows the Bell-Evans-Polanyi principle is designated positive catalysis, whereas when products are obtained from non-Bell-Evans-Polanyi reactivity, it is defined as negative catalysis. In enzymes; however, the first- and second-coordination sphere determines whether positive or negative catalysis happens but many intricate details on how selectivities are reversed are still unknown. In this review paper, we cover recent advances on enzyme understanding where negative catalysis is dominant over positive catalysis. We show that the enzyme can achieve this feat, e.g., through the positioning of substrate and oxidant that then gives the desired product distributions. In particular, often the substrate is positioned such that the desired group of the substrate is placed as close as possible to the oxidant, while unwanted activation channels are blocked by electrostatic perturbations or shielded by protein residues. Furthermore, recent work has shown that reactivity patterns in enzymes can also be influenced by long-range electrostatic interactions like an electric dipole field that can weaken or strengthen chemical bonds through long-range polarization effects. As a result of these electric field effects and long-range electrostatic interactions, enzymes can react through negative catalysis, where a thermodynamically less likely process gives the dominant products. In this review paper, we define and describe positive and negative catalysis in enzymes and compare structure and reactivity with biomimetic and homogeneous catalysts for a number of mononuclear iron-type enzymes including the cytochromes P450 and non-heme iron dioxygenases.

Brownian Dynamics Simulations of Proteins in the Presence of Surfaces: Long-Range Electrostatics and Mean-Field Hydrodynamics.

Simulations of macromolecular diffusion and adsorption in confined environments can offer valuable mechanistic insights into numerous biophysical processes. In order to model solutes at atomic detail on relevant time scales, Brownian dynamics simulations can be carried out with the approximation of rigid body solutes moving through a continuum solvent. This allows the precomputation of interaction potential grids for the solutes, thereby allowing the computationally efficient calculation of forces. However, hydrodynamic and long-range electrostatic interactions cannot be fully treated with grid-based approaches alone. Here, we develop a treatment of both hydrodynamic and electrostatic interactions to include the presence of surfaces by modeling grid-based and long-range interactions. We describe its application to simulate the self-association and many-molecule adsorption of the well-characterized protein hen egg-white lysozyme to mica-like and silica-like surfaces. We find that the computational model can recover a number of experimental observables of the adsorption process and provide insights into their determinants. The computational model is implemented in the Simulation of Diffusional Association (SDA) software package.

Role of Long-Range Electrostatic Interactions and Local Topology of the Hydrogen Bond Network in the Wettability of Fully and Partially Wetted Single and Multilayer Graphene

We report the wetting behavior of graphitic surface–water interfaces through the calculation of the local stress tensor based on the Irving–Kirkwood–Noll theory using detailed atomistic molecular d...

Biophysics of Phase Separation of Disordered Proteins Is Governed by Balance between Short- And Long-Range Interactions.

Intrinsically disordered proteins play a crucial role in cellular phase separation, yet the diverse molecular forces driving phase separation are not fully understood. It is of utmost importance to understand how peptide sequence, and particularly the balance between the peptides’ short- and long-range interactions with other peptides, may affect the stability, structure, and dynamics of liquid–liquid phase separation in protein condensates. Here, using coarse-grained molecular dynamics simulations, we studied the liquid properties of the condensate in a series of polymers in which the ratio of short-range dispersion interactions to long-range electrostatic interactions varied. As the fraction of mutations that participate in short-range interactions increases at the expense of long-range electrostatic interactions, a significant decrease in the critical temperature of phase separation is observed. Nevertheless, sequences with a high fraction of short-range interactions exhibit stabilization, which suggests compensation for the loss of long-range electrostatic interactions. Decreased condensate stability is coupled with decreased translational diffusion of the polymers in the condensate, which may result in the loss of liquid characteristics in the presence of a high fraction of uncharged residues. The effect of exchanging long-range electrostatic interactions for short-range interactions can be explained by the kinetics of breaking intermolecular contacts with neighboring polymers and the kinetics of intramolecular fluctuations. While both time scales are coupled and increase as electrostatic interactions are lost, for sequences that are dominated by short-range interactions, the kinetics of intermolecular contact breakage significantly slows down. Our study supports the contention that different types of interactions can maintain protein condensates, however, long-range electrostatic interactions enhance its liquid-like behavior.

Lattice-gas model of a charge regulated planar surface.

In this work, we consider a lattice-gas model of charge regulation with electrostatic interactions within the Debye-Hückel level of approximation. In addition to long-range electrostatic interactions, the model incorporates the nearest-neighbor interactions for representing non-electrostatic forces between adsorbed ions. The Frumkin-Fowler-Guggenheim isotherm obtained from the mean-field analysis accurately reproduces the simulation data points.

Miniaturized pattern formation in a soft elastically graded thin film in adhesive contact

Self-organization in soft (shear modulus: μ < 1 MPa) thin films (thickness: h < 10 μm) like poly-dimethyl siloxane has been conducive in forming patterns at meso-nano lengthscales. When an elastically inhomogeneous thin film, with depthwise positive shear modulus variation, is near an external contactor, the instabilities ensue at a reduced lengthscale of λc=2.96-0.37logR-0.078Mh compared to λc=2.96h for homogeneous films (R=μbase/μfilm, M slope variation parameter, values of which are 1 and 0 for a homogeneous film). For long-ranged electrostatic interactions, for constant separation distances, the reduced patterns ensue at critical voltages of ~50 V (10 times lower), whereas for constant voltages, dense spiky patterns with 20 times increase in asperity ratio than homogeneous films of similar base modulus are observed in the present numerical studies. All these effects, favourable for creating enhanced functionalized surfaces are relatively more noticeable for those inhomogeneous films which possess high shear modulus gradient ΔμΔz/μ-20 near the free interface.

Equilibrium phase diagram and thermal responses of charged DNA-virus rod-suspensions at low ionic strengths

The collective behavior of DNA is important for exploring new types of bacteria in the means of detection, which is greatly interested in the understanding of interactions between DNAs in living systems. How they self-organize themselves is a physical common phenomenon for broad ranges of thermodynamic systems. In this work, the equilibrium phase diagrams of charged chiral rods (fd viruses) at low ionic strengths (below a few mM) are provided to demonstrate both replicas of (or self-organized) twist orders and replica symmetry breaking near high concentration glass-states. By varying the ionic strengths, it appears that a critical ionic strength is obtained below 1–2 mM salt, where the twist and freezing of nematic domains diverge. Also, the microscopic relaxation is revealed by the ionic strength-dependent effective Debye screening length. At a fixed low ionic strength, the local orientations of twist are shown by two different length scales of optical pitch, in the chiral-nematic N* phase and the helical domains H_{D}, for low and high concentration, respectively. RSB occurs in several cases of crossing phase boundary lines in the equilibrium phase diagram of DNA-rod concentration and ionic strength, including long-time kinetic arrests in the presence of twist orders. The different pathways of PATH I, II and III are due to many-body effects of randomized orientations for charged fd rods undergoing long-range electrostatic interactions in bulk elastic medium. In addition, the thermal stability are shown for chiral pitches of the N* phase and the abnormal cooling process of a specific heat in a structural glass. Here, the concentration-driven twist-effects of charged DNA rods are explored using various experimental methods involving image-time correlation, microscopic dynamics in small angle dynamic light scattering, optical activity in second harmonic generation, and differential scanning calorimetry for the glass state.

Modulating surface interactions for regenerable separation of oil-in-water emulsions

Developing antifouling coatings is of both fundamental and practical significance, but challenging, for membrane separation of oil-in-water (O/W) emulsions with charged surfactants, which has been conventionally achieved through the short-range hydration interaction from hydrophilic membrane surfaces as a physical barrier. Herein, we report a mussel-inspired antifouling coating formed by carboxyl and quaternary ammonium moieties bearing adjustable surface charge property, employing tunable long-range electrostatic interaction to achieve adaptive antifouling performance in response to the varying electrical characteristic of emulsions. The surface force measurement results showed that modulating the surface electrical properties of the coatings through varying the solution pH could effectively alter their electrostatic interactions with emulsions from attraction to repulsion, in combination with hydrodynamic interactions, to enable emulsion repellence of the coatings. Such functional coatings were further applied on a PVDF membrane with an enhanced water permeability and reusability achieved to separate both the positively and negatively charged emulsions. By properly modulating the membrane surface charge, the modified membrane demonstrated its adaptive antifouling performance for efficient and universal water treatment. This work provides useful insights into the antifouling mechanisms of membranes to O/W emulsions, as well as developing functional materials with tunable surface interactions for various engineering applications.

Extended Lagrangian Born–Oppenheimer molecular dynamics for orbital-free density-functional theory and polarizable charge equilibration models

Extended Lagrangian Born-Oppenheimer molecular dynamics (XL-BOMD) [A. M. N. Niklasson, Phys. Rev. Lett. 100, 123004 (2008)] is formulated for orbital-free Hohenberg-Kohn density-functional theory and for charge equilibration and polarizable force-field models that can be derived from the same orbital-free framework. The purpose is to introduce the most recent features of orbital-based XL-BOMD to molecular dynamics simulations based on charge equilibration and polarizable force-field models. These features include a metric tensor generalization of the extended harmonic potential, preconditioners, and the ability to use only a single Coulomb summation to determine the fully equilibrated charges and the interatomic forces in each time step for the shadow Born-Oppenheimer potential energy surface. The orbital-free formulation has a charge-dependent, short-range energy term that is separate from long-range Coulomb interactions. This enables local parameterizations of the short-range energy term, while the long-range electrostatic interactions can be treated separately. The theory is illustrated for molecular dynamics simulations of an atomistic system described by a charge equilibration model with periodic boundary conditions. The system of linear equations that determines the equilibrated charges and the forces is diagonal, and only a single Ewald summation is needed in each time step. The simulations exhibit the same features in accuracy, convergence, and stability as are expected from orbital-based XL-BOMD.

Conformational Motion of Ferredoxin Enables Efficient Electron Transfer to Heme in the Full-Length P450TT.

Cytochrome P450 monooxygenases (P450s) are versatile biocatalysts used in natural products biosynthesis, xenobiotic metabolisms, and biotechnologies. In P450s, the electrons required for O2 activation are supplied by NAD(P)H through stepwise electron transfers (ETs) mediated by redox partners. While much is known about the machinery of the catalytic cycle of P450s, the mechanisms of long-range ET are largely unknown. Very recently, the first crystal structure of full-length P450TT was solved. This enables us to decipher the interdomain ET mechanism between the [2Fe-2S]-containing ferredoxin and the heme, by use of molecular dynamics simulations. In contrast to the "distal" conformation characterized in the crystal structure where the [2Fe-2S] cluster is ∼28 Å away from heme-Fe, our simulations demonstrated a "proximal" conformation of [2Fe-2S] that is ∼17 Å [and 13.7 Å edge-to-edge] away from heme-Fe, which may enable the interdomain ET. Key residues involved in ET pathways and interdomain complexation were identified, some of which have already been verified by recent mutation studies. The conformational transit of ferredoxin between "distal" and "proximal" was found to be controlled mostly by the long-range electrostatic interactions between the ferredoxin domain and the other two domains. Furthermore, our simulations show that the full-length P450TT utilizes a flexible ET pathway that resembles either P450Scc or P450cam. Thus, this study provides a uniform picture of the ET process between reductase domains and heme domain.

Binding of azobenzene andp-diaminoazobenzene to the human voltage-gated sodium channel Nav1.4

The activity of voltage-gated ion channels can be controlled by the binding of photoswitches inside their internal cavity and subsequent light irradiation. We investigated the binding of azobenzene and p-diaminoazobenzene to the human Nav1.4 channel in the inactivated state by means of Gaussian accelerated molecular dynamics simulations and free-energy computations. Three stable binding pockets were identified for each of the two photoswitches. In all the cases, the binding is controlled by the balance between the favorable hydrophobic interactions of the ligands with the nonpolar residues of the protein and the unfavorable polar solvation energy. In addition, electrostatic interactions between the ligand and the polar aminoacids are also relevant for p-diaminoazobenzene due to the presence of the amino groups on the benzene moieties. These groups participate in hydrogen bonding in the most favorable binding pocket and in long-range electrostatic interactions in the other pockets. The thermodinamically preferred binding sites found for both photoswitches are close to the selectivity filter of the channel. Therefore, it is very likely that the binding of these ligands will induce alterations in the ion conduction through the channel.