Point Charge Water Model Research Articles

Thermodynamics of Metal-Acetate Interactions.

Metal ions play crucial roles in protein- and ligand-mediated interactions. They not only act as catalysts to facilitate biological processes but are also important as protein structural elements. Accurately predicting metal ion interactions in computational studies has always been a challenge, and various methods have been suggested to improve these interactions. One such method is the 12-6-4 Lennard-Jones (LJ)-type nonbonded model. Using this model, it has been possible to successfully reproduce the experimental properties of metal ions in aqueous solution. The model includes induced dipole interactions typically ignored in the standard 12-6 LJ nonbonded model. In this we expand the applicability of this model to metal ion-carboxylate interactions. Using 12-6-4 parameters that reproduce the solvation free energies of the metal ions leads to an overestimation of metal ion-acetate interactions, thus, prompting us to fine-tune the model to specifically handle the latter. We also show that the standard 12-6 LJ model significantly falls short in reproducing the experimental binding free energy between acetate and 11 metal ions (Ni(II), Mg(II), Cu(II), Zn(II), Co(II), Cu(I), Fe(II), Mn(II), Cd(II), Ca(II), and Ag(I)). In this study, we describe optimized C4 parameters for the 12-6-4 LJ nonbonded model to be used with three widely employed water models (Transferable Intermolecular Potential with 3 Points (TIP3P), Simple Point Charge Extended (SPC/E), and Optimal Point Charge (OPC) water models). These parameters can accurately match the experimental binding free energy between 11 metal ions and acetate. These parameters can be applied to the study of metalloproteins and transition metal ion channels and transporters, as acetate serves as a representative of the negatively charged amino acid side chains from aspartate and glutamate.

Reactive force field potential with shielded long-range Coulomb interaction: Application to graphene–water capacitors

Electrode–electrolyte interfacial properties characterize the functioning of electrochemical devices, and reactive molecular dynamics simulations, using reactive force fields (ReaxFF) and charge equilibration (QEq) techniques, are classical atomistic methods for investigating the processes that govern the device properties. However, the numerical implementation of ReaxFF and QEq treats Coulomb interaction with a short-distance cutoff for computational speed, thereby limiting interactions among atoms to a domain containing only their neighbor lists. Excluding long-distance Coulomb interactions makes the description of electrostatics in large-scale systems intractable. We apply Ewald sum in the extension of ReaxFF to include long-range Coulomb (LRC) interactions and investigate the effect of the inclusion on the electrostatic and capacitive properties of graphene–water interfaces at different applied potentials in comparison with the original ReaxFF. The study shows that with the inclusion of long-range Coulomb, the capacitance amounts to 4.9 ± 0.2 μF cm−2 compared with 4.4 ± 0.2 μF cm−2 predicted by the original ReaxFF [with short-range Coulomb (SRC)]; thus, indicating that SRC underestimates the capacitance of water between graphene walls by 12% when compared with the 5.0 μF cm−2 predicted with the extended simple point charge (SPC/E) water model. Thus, the results indicate that LRC ReaxFF/QEq have the ability and advantage to model electrochemical processes at a more realistic Coulomb interaction description and foster the processing of the details about the operation of electrochemical devices than the SRC.

Shear viscosity of OPC and OPC3 water models.

Water is a unique and abundant substance in biological and chemical systems. Considering its importance and ubiquity, numerous water models have been developed to reproduce various properties of bulk water in molecular simulations. Therefore, selecting an appropriate water model suitable for the properties of interest is crucial for computational studies of water systems. The four-point Optimal Point Charge (OPC) and three-point OPC (OPC3) water models were developed in 2014 and 2016, respectively. These models reproduce numerous properties of bulk water with high accuracy, such as density, dielectric constant, heat of vaporization, self-diffusion coefficient, and surface tension. In this study, we evaluated the shear viscosities of the OPC and OPC3 water models at various temperatures ranging from 273 to 373K using the Green-Kubo formalism to assess their performance. The evaluated viscosities of both models were very close to each other at all the examined temperatures. At temperatures above 310K, the calculated shear viscosities were in excellent agreement with the experimental results. However, at lower temperatures, the water models systematically underestimated the shear viscosity, with the calculated values at 273 and 298K being 20% and 10% lower than the experimental values, respectively. Despite this limitation, the OPC and OPC3 water models outperformed other widely used water models.

Incorporating Polarization and Charge Transfer into a Point-Charge Model for Water Using Machine Learning

Rigid nonpolarizable water models with fixed point charges have been widely employed in molecular dynamics simulations due to their efficiency and reasonable accuracy for the potential energy surface. However, the dipole moment surface of water is not necessarily well-described by the same fixed charges, leading to failure in reproducing dipole-related properties. Here, we developed a machine-learning model trained against electronic structure data to assign point charges for water, and the resulting dipole moment surface significantly improved the predictions of the dielectric constant and the low-frequency IR spectrum of liquid water. Our analysis reveals that within our atom-centered point-charge description of the dipole moment surface, the intermolecular charge transfer is the major source of the peak intensity at 200 cm-1, whereas the intramolecular polarization controls the enhancement of the dielectric constant. The effects of exact Hartree-Fock exchange in the hybrid density functional on these properties are also discussed.

COMPARATIVE CHAINS DYNAMICS OF TRIOSEPHOSPHATE ISOMERASE INVESTIGATED BY MOLECULAR DYNAMICS SIMULATION

Triosephosphate isomerase is an enzyme which catalyzes the inter-conversion between glyceraldehyde-3-phosphate and dihydroxyacetone phosphate in the fifth step of the glycolytic pathway. In this study, molecular dynamics simulation technique was employed to investigate the dynamics of the two monomer chains of triosephosphate isomerase of trypanosoma brucei brucei (TbTIM) using GROMACS 2016.04 software. The MD simulation of the x-ray structure of TbTIM was performed using the GROMOS 9643a1 force field and simple point charge water model under isothermal-isobaric condition with periodic boundary conditions imposed on x, y, z directions. The Root Mean Square Deviation (RMSD) Root Mean Square fluctuation (RMSF), Radius of Gyration (ROG), Solvent accessible surface area (SASA) and hydrogen bonds were computed. The RMSD values indicate that chain-B shows transition between two conformational states with higher RMSD value of 0.45 nm when compared to chain-A with RMSD of 0.27 nm. The RMSF values indicates that residues of loop 6 (residues 166 to 177) have the highest fluctuations in both chains compared to other residues with chain-A having higher fluctuations peak. The ROG values of chain-A varies from 1.675 nm to 1.761 nm while that of chain-B varies from 2.480 nm to 2.590 nm implying that chain-A is more compact during the simulation than chain-B. The SASA values indicates that chain-B has more contact with solvent than chain-A. 160 hydrogen bonds were found which indicates the stability of the protein during the simulation. From the RMSD, ROG, SASA values, it is evident that chain-B of triosephosphate isomerase of trypanosoma bruceibrucei displayed greater structural dynamics than chain-A during the MD simulation.

Gmak: A Parameter-Space Mapping Strategy for Force-Field Calibration.

In the context of classical molecular simulations, the accuracy of a force field is highly influenced by the values of the relevant simulation parameters. In this work, a parameter-space mapping (PSM) workflow is proposed to aid in the calibration of force-field parameters, based mainly on the following features: (i) regular-grid discretization of the search space; (ii) partial sampling of the search-space grid; (iii) training of surrogate models to predict the estimates of the target properties for nonsampled parameter sets; (iv) post hoc interpretation of the results in terms of multiobjective optimization concepts; (v) attenuation of statistical errors achieved via empiric extension of the duration of the simulations; (vi) iterative search-space translation according to a user-defined scalar objective function that measures the accuracy of the force field (e.g., the weighted root-mean-square deviation of the target properties relative to the reference data). This combination of features results in a hybrid of a single- and a multiobjective optimization strategy, allowing for the approximate determination of both a local minimum of the chosen objective function and its neighboring Pareto efficient points. The PSM workflow is implemented in the extensible Python program gmak, which is made available in the Git repository at http://github.com/mssm-labmmol/gmak. Using this implementation, the PSM workflow was tested in a proof-of-concept fashion in the recalibration of the Lennard-Jones parameters of the 3-point Optimal Point Charge (OPC3) water model for compatibility with the GROMOS treatment of nonbonded interactions. The recalibrated model reproduces typical pure-liquid properties with an accuracy similar to the original OPC3 model and represents a significant improvement relative to the Simple Point Charge (SPC) model, which is the official recommendation for simulations using GROMOS force fields.

Effects of electric field on Rayleigh limit of nanoscale water droplets: molecular dynamics simulation

Nanoscale charged water droplets play a significant role in many physical processes, including cloud electrification and electrospray ionization, which have become one research focus. Generally, the maximum value of charge that a droplet can carry is called Rayleigh limit. Here, we investigate the effect of electric field (<0.5 V nm−1) on Rayleigh limit of nanoscale water droplets (r < 5 nm) by molecular dynamics simulation and theoretically qualitative analysis. In the simulation, Rayleigh limit of nanoscale water droplets under various electric fields is investigated based on optimal point charge water model by GROMACS package code. Our study demonstrates that electric field could affect Rayleigh limit by generating the induced charge, changing the surface tension and the droplet shape. Further, we propose the modified Rayleigh limit formula under electric field, with considering the potential energy of deformed charged droplet under strong electric field. The modified formula can qualitatively explain the abnormal trend that Rayleigh limit of nanoscale water droplet (r > 3 nm) decreases first and then increases with the electric field (<0.5 V nm−1) in the simulation.

On the Choice of Different Water Model in Molecular Dynamics Simulations of Nanopore Transport Phenomena.

The water transport through nanoporous multilayered graphene at 300k is investigated using molecular dynamics (MD) simulation with different water models in this study. We used functionalized and non-functionalized membranes along with five different 3-point rigid water models: SPC (simple point charge), SPC/E (extended simple point charge), TIP3P-FB (transferable intermolecular potential with 3 points-Force Balance), TIP3P-EW (transferable intermolecular potential with 3 points with Ewald summation) and OPC3 (3-point optimal point charge) water models. Based on our simulations with two water reservoirs and a porous multilayered graphene membrane in-between them, it is evident that the water transport varies significantly depending on the water model used, which is in good agreement with previous works. This study contributes to the selection of a water model for molecular dynamics simulations of water transport through multilayered porous graphene.

Diffusion coefficient and solvation free energy of sucrose in water: a molecular dynamics study

In this work, we have carried out Molecular Dynamics Simulation technique to study the diffusion coefficients, radial distribution functions and solvation free energy of sucrose (C12H22O11) at different temperatures ranging from 298.15 K to 318.15 K. We have taken 2 molecules of sucrose in 1343 molecules of extended simple point charge (SPC/E) water model. The self-diffusion coefficients are obtained by applying linear best fit to the mean squaredisplacement (MSD) plot and binary diffusion coefficients are obtained by using Darken’s relation. Arrhenius equation has been used to show a linear relationship between natural logarithm of binary diffusion coefficient and reciprocal of temperature. The structural analysis of the solution has been carried out with the help of radial distribution functions (RDFs) of its constituents. The solvation free energy of sucrose is studied at 300 K by using free energy perturbation method like Bennett Acceptance Ratio (BAR). The results of binary diffusion coefficients obtained from this simulation work agree very well with the previously reported experimental data.

Molecular dynamics simulations of Lithium Fluoride aqueous solutions: Effects of ion concentration on the structural and dynamical properties at T=300 K

Lithium fluoride aqueous system play an important role in a variety of chemical engineering, energy, biochemistry and environmental processes. Lithium salts are also widely used in conventional electrolytes for making lithium-ion batteries. Computer simulation of lithium in fluoride aqueous solution has an important tool in understanding the structural and dynamical characteristics of ionic complexes. In this investigation, the structural and dynamical properties of supersatured LiF systems have been studied by molecular dynamics simulations at different molalities range from 0.05 up to 2.00 mol.Kg-1 using extended simple point charge (SPC/E) water model and the ions which are modeled as charged Lennard-Jones particles. Molecular dynamics simulations return highly complex data. The cartesian positions of each atom of lithium chloride aqueous solution are recorded at every time step of the trajectory. Therefore, the analysis of data requires to calculate the radial distribution functions (RDFs) describing the structure of the hydration shells around the ions in solutions and the hydration number. The structural properties of the water and Li+ and F- ions, such as the coordination number, interparticle distance, self-diffusion coefficient and dielectric constant are strongly depending on the molality and chemical nature of counterions.

When do short-range atomistic machine-learning models fall short?

We explore the role of long-range interactions in atomistic machine-learning models by analyzing the effects on fitting accuracy, isolated cluster properties, and bulk thermodynamic properties. Such models have become increasingly popular in molecular simulations given their ability to learn highly complex and multi-dimensional interactions within a local environment; however, many of them fundamentally lack a description of explicit long-range interactions. In order to provide a well-defined benchmark system with precisely known pairwise interactions, we chose as the reference model a flexible version of the Extended Simple Point Charge (SPC/E) water model. Our analysis shows that while local representations are sufficient for predictions of the condensed liquid phase, the short-range nature of machine-learning models falls short in representing cluster and vapor phase properties. These findings provide an improved understanding of the role of long-range interactions in machine learning models and the regimes where they are necessary.

Diffusion of oxytocin in water: a molecular dynamics study

Classical molecular dynamics simulation is performed to estimate the diffusion coefficient of oxytocin in water at different temperatures, 288 K, 300 K, 313 K, 323 K, using GROningen Machine for Chemical Simulations (GROMOCS). The simulation is carried out using GROMOS43A1 force field and extended simple point charge (SPC/E) water model. The stability of the system is evaluated from energy profile of potential and kinetic energy, which assures well equilibrated molecular system. The self-diffusion coefficient of oxytocin and water is obtained from Einstein’s relation and binary diffusion coefficient is obtained from Darken’s relation. As temperature increases the diffusion coefficient also increases as per expectation. The diffusion coefficients of water from the present calculations agree well with the previously reported values, within the 10% of deviation. Furthermore, the activation energy has been studied using Arrhenius Plot.&#x0D; BIBECHANA 18 (2021) 108-117

Molecular dynamics study of confined water in the periclase-brucite system under conditions of reaction-induced fracturing

The volume-increase associated with hydration reactions in rocks may lead to reaction-induced fracturing, but requires a stable water film to be present at reactive grain boundaries even when subject to compressive stress. Hydration of periclase to brucite is associated with a solid volume increase of ca. 110%. Recent experiments on the periclase-brucite system observed that when the effective mean stress exceeds 30 MPa, the reaction rate slows down dramatically. We hypothesize that for the brucite forming reaction to progress, the fluid film between grains must remain stable. If the applied pressure becomes larger than the hydration force, the fluid film will collapse and be squeezed out of the grain contacts. To quantify this effect, we study the behavior of a water film confined between periclase or brucite surfaces subject to compressive stress, by performing molecular dynamics simulations. The simulations are carried out using the ClayFF force field and the single point charge (SPC) water model in the molecular dynamics simulations program LAMMPS. The setup consists of two interfaces of either periclase or brucite surrounded by water. Our simulations show that when the pressure reaches a few tens of MPa, the water film collapses and reduces the water film to one or two water layers, while the self-diffusion coefficient of water molecules by a factor of eight. A water film thickness below two water layers is thinner than the size of the hydration shell around Mg2+-ions, which will limit ion-transport. The observed collapse of the water film to a single layer at a normal pressure of 25–30 MPa might explain the observed slow-down of reaction-induced fracturing in the periclase-brucite system.

Combined effect of weak electric field and ions on critical water cluster: Insight from molecular dynamics simulation

The effects of ion and electric field on the vapor–liquid transition of water, are studied by using the optimal point charge (OPC) water model in this paper. A canonical Molecular Dynamics (MD) simulation approach, which calculates equilibrium time and the number of water molecules in the clusters, is employed to study the factors affecting the nucleation of water molecules. In addition, Quantum Mechanics (QM) method is adopted to calculate the hydration free energy of ions as a supplement. The results demonstrate that the ion has a significant promoting effect on vapor–liquid nucleation below the critical nucleus size (1–3 nm). However, as the cluster grows, the ion will no longer promote cluster growth, due to electrostatic shielding effect from the aggregated water molecules. When a weak uniform electric field (less than 0.1 V/nm) is applied, the promotion of the ion reappears. According to the trajectory analysis of ion in the water droplet, we believe that the electric field changes the relative position of ions in the droplets, thus weakening the shielding of water molecules. It is further demonstrated by a proposed novel statistical method, which provides an alternative, visualized and effective approach to evaluate the promotion effect in similar analyses, compared to radial distribution function.

Short solvent model for ion correlations and hydrophobic association

Coulomb interactions play a major role in determining the thermodynamics, structure, and dynamics of condensed-phase systems, but often present significant challenges. Computer simulations usually use periodic boundary conditions to minimize corrections from finite cell boundaries but the long range of the Coulomb interactions generates significant contributions from distant periodic images of the simulation cell, usually calculated by Ewald sum techniques. This can add significant overhead to computer simulations and hampers the development of intuitive local pictures and simple analytic theory. In this paper, we present a general framework based on local molecular field theory to accurately determine the contributions from long-ranged Coulomb interactions to the potential of mean force between ionic or apolar hydrophobic solutes in dilute aqueous solutions described by standard classical point charge water models. The simplest approximation leads to a short solvent (SS) model, with truncated solvent-solvent and solute-solvent Coulomb interactions and long-ranged but screened Coulomb interactions only between charged solutes. The SS model accurately describes the interplay between strong short-ranged solute core interactions, local hydrogen-bond configurations, and long-ranged dielectric screening of distant charges, competing effects that are difficult to capture in standard implicit solvent models.

Wetting Properties of the CO2-Water-Calcite System via Molecular Simulations: Shape and Size Effects.

Assessment of the risks and environmental impacts of carbon geosequestration requires knowledge about the wetting behavior of mineral surfaces in the presence of CO2 and the pore fluids. In this context, the interfacial tension (IFT) between CO2 and the aqueous fluid and the contact angle, θ, with the pore mineral surfaces are the two key parameters that control the capillary pressure in the pores of the candidate host rock. Knowledge of these two parameters and their dependence on the local conditions of pressure, temperature, and salinity is essential for the correct prediction of structural and residual trapping. We have performed classical molecular dynamics simulations to predict the CO2-water IFT and the CO2-water-calcite contact angle. The IFT results are consistent with previous simulations, where simple point charge water models have been shown to underestimate the water surface tension, thus affecting the simulated IFT values. When combined with the EPM2 CO2 model, the SPC/Fw water model indeed underestimates the IFT in the low-pressure region at all temperatures studied. On the other hand, at high pressure and low temperature, the IFT is overestimated by ∼5 mN/m. Literature data regarding the CO2/water/calcite contact angle on calcite are contradictory. Using our new set of force field parameters, we performed NVT simulations at 323 K and 20 MPa to calculate the contact angle of a water droplet on the calcite {10.4} surface in a CO2 atmosphere. We performed simulations for both spherical and cylindrical droplet configurations for different initial radii to study the size dependence of the water contact angle on calcite in the presence of CO2. Our results suggest that the contact angle of a cylindrical droplet, is independent of droplet size, for droplets with a radius of 50 Å or more. On the contrary, spherical droplets make a contact angle that is strongly influenced by their size. At the largest size explored in this study, both spherical and cylindrical droplets converge to the same contact angle, 38°, indicating that calcite is strongly wetted by water.

Systematic Design-of-Experiments, factorial-design approaches for tuning simple empirical water models

ABSTRACT Using systematic Design-of-Experiments, factorial-design approaches, we identify how five variables (site charge, sigma, epsilon, OH bond length and HOH bond angle) affect the diffusivity and radial distribution function accuracy within the framework of the Simple Point Charge water model. From this (by a full-functional DoX-effects model), we glean response equations for the effects of these systematic variations on both estimation of site-site radial distribution functions, in addition to self-diffusivities, allowing scope to estimate more precisely optimal parameters for use in tailored force-fields for particular purposes (e.g. improved fidelity towards particular desired structural or dynamical properties). To this end, the diffusivity error was reduced from an initial value of 35.2–0.64%, whilst the radial distribution function was more difficult to improve, with a reduction in error of 2.83%.

Compatibility of GROMOS-Derived Atomic Parameters for Lipopolysaccharide Membranes with the SPC/E Water Model and Alternative Long-Range Electrostatic Treatments Using Single Nonbonded Cutoff and Atom-Based Charge Schemes

Recent developments of GROMACS v.2016 ceased to support methodological approaches used in the development and validation of the GROMOS force field. We investigated the performance of a previously developed extension of the GROMOS force field for lipopolysaccharides to reproduce the structural dynamics of bacterial outer membrane (OM) using a single cutoff for nonbonded interactions and atom-based charge truncation. We further compared this setup for use with reaction field (RF) or particle mesh Ewald (PME) approximations in the presence of simple point charge (SPC) and extended simple point charge (SPC/E) water models. We find that the OM structural dynamics is well conserved in all simulated conditions, reproducing the available experimental data within the measurement uncertainty. The SPC/E model induces a small increase in OM fluidity, and when combined with the RF correction, shows a decrease in water orientation at the membrane surface. The present simulations support the compatibility of the GROMOS-derived lipopolysaccharide (LPS) parameters for use with single cutoff and atom-based charge schemes, either with RF or PME approximations, in GROMACS v.2016. Both SPC and SPC/E water models are suitable for use, but usage of SPC/E combined with the reaction field correction needs to be further investigated.

All-atom computations with irreversible Markov chains.

We apply the irreversible event-chain Monte Carlo (ECMC) algorithm to the simulation of dense all-atom systems with long-range Coulomb interactions. ECMC is event-driven and exactly samples the Boltzmann distribution. It neither uses time-step approximations nor spatial cutoffs on the range of the interaction potentials. Most importantly, it need not evaluate the total Coulomb potential and thus circumvents the major computational bottleneck of traditional approaches. It only requires the derivatives of the two-particle Coulomb potential, for which we discuss mutually consistent choices. ECMC breaks up the total interaction potential into factors. For particle systems made up of neutral dipolar molecules, we demonstrate the superior performance of dipole-dipole factors that do not decompose the Coulomb potential beyond the two-molecule level. We demonstrate that these long-range factors can nevertheless lead to local lifting schemes, where subsequently moved particles are mostly close to each other. For the simple point-charge water model with flexible molecules (SPC/Fw), which combines the long-ranged intermolecular Coulomb potential with hydrogen-oxygen bond-length vibrations, a flexible hydrogen-oxygen-hydrogen bond angle, and Lennard-Jones oxygen-oxygen potentials, we break up the potential into factors containing between two and six particles. For this all-atom liquid-water model, we demonstrate that the computational complexity of ECMC scales very well with the system size. This is achieved in a pure particle-particle framework, without the interpolating mesh required for the efficient implementation of other modern Coulomb algorithms. Finally, we discuss prospects and challenges for ECMC and outline several future applications.

Absolute proton hydration free energy, surface potential of water, and redox potential of the hydrogen electrode from first principles: QM/MM MD free-energy simulations of sodium and potassium hydration.

The absolute intrinsic hydration free energy GH+,wat◦ of the proton, the surface electric potential jump χwat◦ upon entering bulk water, and the absolute redox potential VH+,wat◦ of the reference hydrogen electrode are cornerstone quantities for formulating single-ion thermodynamics on absolute scales. They can be easily calculated from each other but remain fundamentally elusive, i.e., they cannot be determined experimentally without invoking some extra-thermodynamic assumption (ETA). The Born model provides a natural framework to formulate such an assumption (Born ETA), as it automatically factors out the contribution of crossing the water surface from the hydration free energy. However, this model describes the short-range solvation inaccurately and relies on the choice of arbitrary ion-size parameters. In the present study, both shortcomings are alleviated by performing first-principle calculations of the hydration free energies of the sodium (Na+) and potassium (K+) ions. The calculations rely on thermodynamic integration based on quantum-mechanical molecular-mechanical (QM/MM) molecular dynamics (MD) simulations involving the ion and 2000 water molecules. The ion and its first hydration shell are described using a correlated ab initio method, namely resolution-of-identity second-order Møller-Plesset perturbation (RIMP2). The next hydration shells are described using the extended simple point charge water model (SPC/E). The hydration free energy is first calculated at the MM level and subsequently increased by a quantization term accounting for the transformation to a QM/MM description. It is also corrected for finite-size, approximate-electrostatics, and potential-summation errors, as well as standard-state definition. These computationally intensive simulations provide accurate first-principle estimates for GH+,wat◦, χwat◦, and VH+,wat◦, reported with statistical errors based on a confidence interval of 99%. The values obtained from the independent Na+ and K+ simulations are in excellent agreement. In particular, the difference between the two hydration free energies, which is not an elusive quantity, is 73.9 ± 5.4 kJ mol-1 (K+ minus Na+), to be compared with the experimental value of 71.7 ± 2.8 kJ mol-1. The calculated values of GH+,wat◦, χwat◦, and VH+,wat◦ (-1096.7 ± 6.1 kJ mol-1, 0.10 ± 0.10 V, and 4.32 ± 0.06 V, respectively, averaging over the two ions) are also in remarkable agreement with the values recommended by Reif and Hünenberger based on a thorough analysis of the experimental literature (-1100 ± 5 kJ mol-1, 0.13 ± 0.10 V, and 4.28 ± 0.13 V, respectively). The QM/MM MD simulations are also shown to provide an accurate description of the hydration structure, dynamics, and energetics.