Titers of IgG and IgA against SARS-CoV-2 proteins and their association with symptoms in mild COVID-19 infection.

Humoral immunity in COVID-19 includes antibodies (Abs) targeting spike (S) and nucleocapsid (N) SARS-CoV-2 proteins. Antibody levels are known to correlate with disease severity, but titers are poorly reported in mild or asymptomatic cases. Here, we analyzed the titers of IgA and IgG against SARS-CoV-2 proteins in samples from 200 unvaccinated Hospital Workers (HWs) with mild COVID-19 at two time points after infection. We analyzed the relationship between Ab titers and patient characteristics, clinical features, and evolution over time. Significant differences in IgG and IgA titers against N, S1 and S2 proteins were found when samples were segregated according to time T1 after infection, seroprevalence at T1, sex and age of HWs and symptoms at infection. We found that IgM + samples had higher titers of IgG against N antigen and IgA against S1 and S2 antigens than IgM - samples. There were significant correlations between anti-S1 and S2 Abs. Interestingly, IgM + patients with dyspnea had lower titers of IgG and IgA against N, S1 and S2 than those without dyspnea. Comparing T1 and T2, we found that IgA against N, S1 and S2 but only IgG against certain Ag decreased significantly. In conclusion, an association was established between Ab titers and the development of infection symptoms.

Reversible and efficient SO2 capture by a chemically stable MOF CAU-10: experiments and simulations.

The adsorption of sulphur dioxide (SO2) in CAU-10 is obtained with the use of advanced experimental and computational tools to gain insight into the molecular mechanisms responsible for the adsorption of SO2. It is shown that the adsorption by CAU-10 is highly energy efficient and that van der Waals interactions are the driving force that controls adsorption in this system.

Parametrization with Explicit Water of Solvents Used in Lithium-Ion Batteries: Cyclic Carbonates and Linear Ethers.

Molecular dynamics simulations are performed to study carbonates and ethers that are widely used as electrolytes in energy storage devices. The first type contains in their molecular geometry a hydrocarbon tail of ethylene, propylene, and butylene whereas in the second type, the tail comprises 1,2-dimethoxyethane and 1,2-diethoxyethane. The evaluation of optimized potential for liquid simulations (OPLS), CHARMM, and GROMOS force fields for some of the solvents shows poor agreement with experimental thermodynamic and transport properties leading us to parameterize those solvents using the OPLS parameters as the starting point. A systematic procedure that uses the solubility of the solvents as the target property in simulations with explicit water is applied. The transferability of the parameters of the smallest cyclic or linear molecules was used to simulate systems with longer hydrocarbon chains. The optimized parameter reproduce the experimental solubility of butylene carbonate and 1,2-diethoxyethane in water. The interaction parameters were used to obtain the self-diffusion coefficients of ions of the salt LiPF6 at 1 M concentration in mixtures with ethylene carbonate or propylene carbonate. The simulation results for pure components and mixtures with the new parameters are in excellent agreement with the experimental data.

Constrained dipole moment density functional theory for charge distributions in force fields for the study of molecular fluids.

A new procedure, based on electronic structure calculations that only requires a dipole moment value for a given molecule as input and, from which the charges for all the atoms in it are uniquely determined, is developed and applied to the study of molecular fluids with classical dynamics. The dipole moment value considered for the isolated molecule is the one that reproduces the dielectric constant of its corresponding fluid. Following previous work, the Lennard-Jones parameters are determined to reproduce the liquid density and the surface tension at the liquid-vapor interface. The force field thus obtained leads to a reasonable description of several properties such as heats of vaporization, self-diffusion coefficients, shear viscosities, isothermal compressibilities, and volumetric expansion coefficients of pure substances.

Force Field Parametrization from the Hirshfeld Molecular Electronic Density.

The Hirshfeld charges are linearly increased to reproduce the experimental dielectric constant of 10 polar solvents having values between 13 (pyridine) and 182 ( N-methylformamide). The OPLS/AA force field is used to obtain the new parameters. The surface tension and liquid density are also target properties to determine the new nonbonding parameters. The charge scaling factor is between 1.2 and 1.3. In addition, properties that were not used in the parametrization procedure, such as the heat of vaporization, self-diffusion coefficient, shear viscosity, isothermal compressibility, and volumetric expansion coefficient are obtained. Binary mixtures of amide/water and amide/amide are also studied. The original parameters of OPLS/AA, CGenFF, and GAFF force fields are evaluated. The TIP4P/ε force field is used to simulate water. The results from this work with the new parameters, for both pure components and binary mixtures, are in better agreement with experimental data than those obtained with the original values for most of the calculated properties. The maximum density of N-methylformamide in aqueous solutions is correctly predicted only with the new parameters. The high value of the dielectric constant of acetamide, formamide, and N-methylformamide is discussed in terms of the chain formation from the hydrogen bond interactions.

Force Field Benchmark of the TraPPE_UA for Polar Liquids: Density, Heat of Vaporization, Dielectric Constant, Surface Tension, Volumetric Expansion Coefficient, and Isothermal Compressibility.

The transferable potential for a phase equilibria force field in its united-atom version, TraPPE_UA, is evaluated for 41 polar liquids that include alcohols, thiols, ethers, sulfides, aldehydes, ketones, and esters to determine its ability to reproduce experimental properties that were not included in the parametrization procedure. The intermolecular force field parameters for pure components were fit to reproduce experimental boiling temperature, vapor-liquid coexisting densities, and critical point (temperature, density, and pressure) using Monte Carlo simulations in different ensembles. The properties calculated in this work are liquid density, heat of vaporization, dielectric constant, surface tension, volumetric expansion coefficient, and isothermal compressibility. Molecular dynamics simulations were performed in the gas and liquid phases, and also at the liquid-vapor interface. We found that relative error between calculated and experimental data is 1.2% for density, 6% for heat of vaporization, and 6.2% for surface tension, in good agreement with the experimental data. The dielectric constant is systematically underestimated, and the relative error is 37%. Evaluating the performance of the force field to reproduce the volumetric expansion coefficient and isothermal compressibility requires more experimental data.

Systematic procedure to parametrize force fields for molecular fluids.

A new strategy to develop force fields for molecular fluids is presented. The intermolecular parameters are fitted to reproduce experimental values of target properties at ambient conditions and also the critical temperature. The partial charges are chosen to match the dielectric constant. The Lennard-Jones parameters, εii and σii, are fitted to reproduce the surface tension at the vapor-liquid interface and the liquid density, respectively. The choice of those properties allows obtaining systematically the final parameters using a small number of simulations. It is shown that the use of surface tension as a target property is better than the choice of heat of vaporization. The method is applied to molecules, from all atoms to a coarse-grained level, such as pyridine, dichloromethane, methanol, and 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIM-BF4) at different temperatures and pressures. The heat of vaporization, radial distribution functions, and self-diffusion coeficient are also calculated.

A new force field of formamide and the effect of the dielectric constant on miscibility.

Current force fields underestimate significantly the dielectric constant of formamide at standard conditions. We present a derivation of an accurate potential for formamide, with a functional form based on the OPLS/AA force field. Our procedure follows the approach introduced by Salas et al. ( J. Chem. Theory Comput. 2015 , 11 , 683 - 693 ) that relies on ab initio calculations and molecular dynamics simulations. We consider several strategies to derive the atomic charges of formamide. We find that the inclusion of polarization effects in the quantum mechanical computations is essential to obtain reliable force fields. By varying the atomic charges and the Lennard-Jones parameters describing the dispersion interactions in the OPLS/AA force field, we derive an optimum set of parameters that provides accurate results for the dielectric constant, surface tension, and bulk density of liquid formamide in a wide range of thermodynamic states. We test the transferability of our parameters to investigate liquid/liquid mixtures. We have chosen as case study an equimolar mixture of formamide and hexan-2-one. This mixture involves two fluids with very different polar characteristics, namely, large differences in their dielectric constants and their performance as solvents. The new potential predicts a liquid/liquid phase separation, in good agreement with experimental data, and highlights the importance of the correct parametrization of the pure liquid phases to investigate liquid mixtures. Finally, we examine the microscopic origin of the observed inmiscibility between formamide and hexa-2-one.

Direct Coexistence Methods to Determine the Solubility of Salts in Water from Numerical Simulations. Test Case NaCl.

The solubility of NaCl, an equilibrium between a saturated solution of ions and a solid with a crystalline structure, was obtained from molecular dynamics simulations using the SPC/E and TIP4P-Ew water models. Four initial setups on supersaturated systems were tested on sodium chloride (NaCl) solutions to determine the equilibrium conditions and computational performance: (1) an ionic solution confined between two crystal plates of periodic NaCl, (2) a solution with all the ions initially distributed randomly, (3) a nanocrystal immersed in pure water, and (4) a nanocrystal immersed in an ionic solution. In some cases, the equilibration of the system can take several microseconds. The results from this work showed that the solubility of NaCl was the same, within simulation error, for the four setups, and in agreement with previously reported values from simulations with the setup (1). The system of a nanocrystal immersed in supersaturated solution was found to equilibrate faster than others. In agreement with laser-Doppler droplet measurements, at equilibrium with the solution the crystals in all the setups had a slight positive charge.

Fluid-solid coexistence from two-phase simulations: binary colloidal mixtures and square well systems.

Molecular dynamics simulations are performed to clarify the reasons for the disagreement found in a previous publication [G. A. Chapela, F. del Río, and J. Alejandre, J. Chem. Phys. 138(5), 054507 (2013)] regarding the metastability of liquid-vapor coexistence on equimolar charged binary mixtures of fluids interacting with a soft Yukawa potential with κσ = 6. The fluid-solid separation obtained with the two-phase simulation method is found to be in agreement with previous works based on free energy calculations [A. Fortini, A.-P. Hynninen, and M. Dijkstra, J. Chem. Phys. 125, 094502 (2006)] only when the CsCl structure of the solid is used. It is shown that when pressure is increased at constant temperature, the solids are amorphous having different structures, densities, and the diagonal components of the pressure tensor are not equal. A stable low density fluid-solid phase separation is not observed for temperatures above the liquid-vapor critical point. In addition, Monte Carlo and discontinuous molecular dynamics simulations are performed on the square well model of range 1.15σ. A stable fluid-solid transition is observed above the vapor-liquid critical temperature only when the solid has a face centered cubic crystalline structure.

Non-polarizable force field of water based on the dielectric constant: TIP4P/ε.

The static dielectric constant at room temperature and the temperature of maximum density are used as target properties to develop, by molecular dynamics simulations, the TIP4P/ε force field of water. The TIP4P parameters are used as a starting point. The key step, to determine simultaneously both properties, is to perform simulations at 240 K where a molecular dipole moment of minimum density is found. The minimum is shifted to larger values of µ as the distance between the oxygen atom and site M, lOM, decreases. First, the parameters that define the dipole moment are adjusted to reproduce the experimental dielectric constant and then the Lennard-Jones parameters are varied to match the temperature of maximum density. The minimum on density at 240 K allows understanding why reported TIP4P models fail to reproduce the temperature of maximum density, the dielectric constant, or both properties. The new model reproduces some of the thermodynamic and transport anomalies of water. Additionally, the dielectric constant, thermodynamics, and dynamical and structural properties at different temperatures and pressures are in excellent agreement with experimental data. The computational cost of the new model is the same as that of the TIP4P.

Liquid-vapor phase diagram and surface properties in oppositely charged colloids represented by a mixture of attractive and repulsive Yukawa potentials.

The liquid-vapor phase diagrams of equal size diameter σ binary mixtures of screened potentials have been reported for several ranges of interaction using Monte Carlo simulation methods [J. B. Caballero, A. M. Puertas, A. Fernandez-Barbero, F. J. de las Nieves, J. M. Romero-Enrique, and L. F. Rull, J. Chem. Phys. 124, 054909 (2006); A. Fortini, A.-P. Hynninen, and M. Dijkstra, J. Chem. Phys. 125, 094502 (2006)]. Both works report controversial results about the stability of the phase diagram with the inverse Debye screening length κ. Caballero found stability for values of κσ up to 20 while Fortini reported stability for κσ up to 20 while Fortini reported stability for κσ ≤ 4. In this work a spinodal decomposition process where the liquid and vapor phases coexist through an interface in a slab geometry is used to obtain the phase equilibrium and surface properties using a discontinuous molecular dynamics simulations for mixtures of equal size particles carrying opposite charge and interacting with a mixture of attractive and repulsive Yukawa potentials at different values of κσ. An crude estimation of the triple point temperatures is also reported. The isothermal-isobaric method was also used to determine the phase stability using one phase simulations. We found that liquid-vapor coexistence is stable for values of κσ > 20 and that the critical temperatures have a maximum value at around κσ = 10, in agreement with Caballero et al. calculations. There also exists a controversy about the liquid-vapor envelope stability of the pure component attractive Yukawa model which is also discussed in the text. In addition, details about the equivalence between continuous and discontinuous molecular dynamics simulations are given, in the Appendix, for Yukawa and Lennard-Jones potentials.

Surface Tension of Organic Liquids Using the OPLS/AA Force Field.

Molecular dynamics simulations are performed to obtain the surface tension of 61 organic liquids using the OPLS/AA (all-atom optimized potential for liquid simulations). The force field parameters are the same as those recently used (Caleman et al. J. Chem. Theory Comput.2012, 8, 61) to determine several thermodynamic properties of 146 organic liquids. The correct evaluation of surface tension using slab simulations of liquids requires one to properly take into account the long-range interactions (Trukhymchuk and Alejandre J. Chem. Phys.1999, 111, 8510). In addition, the liquid density from slab simulations has to be the same as that obtained in liquid simulations at constant temperature and pressure. The new results of surface tensions from this work improve those reported by Caleman et al. The OPLS/AA force field gives good surface tensions compared with experimental data for most of the systems studied in this work, although it was developed to simulate liquids.

Surface tension and phase coexistence for fluids of molecules with extended dipoles.

Molecular dynamics simulations of fluids of molecules with extended dipoles were performed, with increasing distance between point charges but with a constant dipole moment, to obtain thermodynamic properties. It was found that the effect of varying the dipole length on the dielectric constant in the liquid phase, the vapor-liquid equilibria, and the surface tension was negligible for dipolar lengths up to half the particle diameter. By comparing thermodynamic properties of the predictions of the extended dipole model with those for the Stockmayer fluid of point dipoles, it was found that extended dipoles are equivalent to point dipoles over a wide range of dipole lengths, and not only near the point dipole limit, when the separation length is very small compared with the mean distance between particles. Finally, phase equilibrium results of extended dipoles were compared to those obtained from the discrete perturbation theory for a Stockmayer potential.

Liquid-vapor phase diagram and cluster formation of two-dimensional ionic fluids.

Direct molecular dynamics simulations on interfaces at constant temperature are performed to obtain the liquid-vapor phase diagram of the two-dimensional soft primitive model, an equimolar mixture of equal size spheres carrying opposite charges. Constant temperature and pressure simulations are also carried out to check consistency with interface simulations results. In addition, an analysis of the cluster formation of mixtures of particles with charge asymmetry in the range 1:1 to 1:36 at low and high densities is performed. The number of free ions, when plotted as a function of the positive ion charge, Z(+), has an oscillatory behavior and is independent of the density. The formation of aggregates is analyzed in terms of the attraction and repulsion between ions.

A non-polarizable model of water that yields the dielectric constant and the density anomalies of the liquid: TIP4Q.

A four-site rigid water model is presented, whose parameters are fitted to reproduce the experimental static dielectric constant at 298 K, the maximum density of liquid water and the equation of state at low pressures. The model has a positive charge on each of the three atomic nuclei and a negative charge located at the bisector of the HOH bending angle. This charge distribution allows increasing the molecular dipole moment relative to four-site models with only three charges and improves the liquid dielectric constant at different temperatures. Several other properties of the liquid and of ice Ih resulting from numerical simulations with the model are in good agreement with experimental values over a wide range of temperatures and pressures. Moreover, the model yields the minimum density of supercooled water at 190 K and the minimum thermal compressibility at 310 K, close to the experimental values. A discussion is presented on the structural changes of liquid water in the supercooled region where the derivative of density with respect to temperature is a maximum.

Liquid-vapor interfacial properties of vibrating square well chains.

Liquid-vapor interfacial properties of square well chains are calculated. Surface tension, orthobaric densities, and vapor pressures are reported. Spinodal decomposition with a discontinuous molecular dynamics simulation program is used to obtain the results which are compared to previously published data for orthobaric densities and vapor pressures. In order to analyze the effect of the chain stiffness results for near tangent and overlapping linear chains as well as angled chains are obtained. Properties are calculated for linear chains of 2, 4, and 8 spheres for intramolecular distances of 0.97, 0.6, and 0.4 as well as for angled chains of 4 and 8 spheres and intramolecular distances of 0.4. The complete series of fully flexible near tangent square well chains is also studied (chains of 2, 4, 8, 12, and 16 particles with intramolecular distances of 0.97). The corresponding states principle applies to most of the systems considered. Critical properties values are reported as obtained from orthobaric densities, surface tensions, and vapor pressures. For the near tangent chains the critical temperatures increase with chain length but the rate of increment tends to zero for the longest chains considered. When the stiffness of the chain increases (intramolecular distance from 1 , 0.6, and 0.4) this saturation effect is either not present or reverses itself. The surface tension increases with the length of the chain while the width of the interface decreases.

Molecular association of heteronuclear vibrating square-well dumbbells in liquid-vapor phase equilibrium.

Molecular aggregates are formed by heteronuclear vibrating square-well dumbbells. In a recent article [G. A. Chapela and J. Alejandre, J. Chem. Phys., 132(10), 104704 (2010)], it is shown that heteronuclear vibrating square-well dumbbells with a diameter ratio between particles of 1/2 and interacting potential ratio of 4 form micelles of different sizes and shapes which manifest themselves in both the liquid and vapor phases, up to and above the critical point. This means that micellization and phase separation are present simultaneously in this simple model. These systems present a maximum in the critical temperature when plotted against the potential well depth of the second particle ε(2). In the same publication, it was speculated that the formation of micelles was responsible for the appearance of the maximum. A thorough study on this phenomena is presented here and it is found that there is a threshold on the size of the second particle and its corresponding depth of interaction potential, where the micelles are formed. If the diameter and well depth of the second particle are small enough for the first and deep enough for the second, micelles are formed. For σ(2)/σ(1) between 0.25 and 0.65 and ε(2)/ε(1) larger than 5.7, micelles are formed up to and above the critical temperature. Outside these ranges micelles appear only at temperatures lower than the critical point. There is a strong temperature dependence on the formation and persistence of the aggregates. For the deepest wells and large enough second particles, a gel interconnected aggregate is obtained. In this work, the micelles are formed at temperatures as low as the triple point and as high as the critical point and, in some cases, persist well above it. The presence of these maxima in critical temperatures T(c) when plotted against ε(2) as follows. At lower values of ε(2), an increase of T(c) is obtained as is expected by the increase of the attractive volume as indicated by the principle of corresponding states. As ε(2) increases further, the formation of molecular aggregates produce a saturation effect of the deepening of the potential well by encapsulating the particles of the second kind inside the micelles, so the resulting T(c) represents a new poly disperse system of molecular aggregates and not the original heteronuclear vibrating square-well dumbbells. The surface tension is also analyzed for these systems, and it is shown that decreases with increasing attraction due to the formation of molecular aggregates.

Discrete perturbation theory applied to Lennard-Jones and Yukawa potentials.

Discrete perturbation theory (DPT) is a powerful tool to study systems interacting with potentials that are continuous but can be approximated by a piecewise continuous function composed of horizontal segments. The main goal of this work is to analyze the effect of several variables to improve the representation of continuous potentials in order to take advantage of DPT. The main DPT parameters chosen for the purpose are the starting location and size of the horizontal segments used to divide the full range of the potential and its maximum reach. We also studied the effect of having each segment aligned to the left, to the right, or centered on the continuous function. The properties selected to asses the success of this strategy are the orthobaric densities and their corresponding critical points. Critical parameters and orthobaric densities were evaluated by DPT for each of an ample set of variables and compared with their values calculated via discontinuous molecular dynamics. The best sets of DPT parameters are chosen so as to give equations of state that represent accurately the Lennard-Jones and Yukawa fluids.

Surface tension and orthobaric densities for vibrating square well dumbbells. I.

Surface tensions and liquid-vapor orthobaric densities are calculated for a wide variety of vibrating square well dumbbells using discontinuous molecular dynamics simulations. The size of the vibration well, the elongation or bond distance of the two particles of the dumbbell, the asymmetry in size (and interaction range) of the two particles, and the depth of the interaction well are the variables whose effects are systematically evaluated in this work. Extensive molecular dynamics simulations were carried out and the orthobaric liquid-vapor densities are compared with those obtained previously by other authors using different methods of simulation for rigid and vibrating square well dumbbells. Surface tension values are reported for the first time for homonuclear and heteronuclear vibrating square well dumbbells as well as for all the simulated series. The molecular dynamics results of tangent homonuclear dumbbells are compared with those from Monte Carlo simulations also obtained in this work, as a way of checking the order of magnitude of the molecular dynamics results. The size of the vibration well is shown to have a small influence on the resulting properties. Decreasing elongation and the size of the second particle increase critical temperatures, liquid densities, and surface tensions. Moderate increases in the depth of the interaction well have the same effect. For larger asymmetries of the depth of the interaction well on the dumbbell particles, a strong association phenomenon is observed and the main effects are a maximum on the critical temperature for increasing well depth and a decrease in the surface tension.