Polarizable Force Field Research Articles

Effect of the QM Size, Basis Set, and Polarization on QM/MM Interaction Energy Decomposition Analysis.

Herein, an Energy Decomposition Analysis (EDA) scheme extended to the framework of QM/MM calculations in the context of electrostatic embeddings (QM/MM-EDA) including atomic charges and dipoles is applied to assess the effect of the QM region size on the convergence of the different interaction energy components, namely, electrostatic, Pauli, and polarization, for cationic, anionic, and neutral systems interacting with a strong polar environment (water). Significant improvements are found when the bulk solvent environment is described by a MM potential in the EDA scheme as compared to pure QM calculations that neglect bulk solvation. The predominant electrostatic interaction requires sizable QM regions. The results reported here show that it is necessary to include a surprisingly large number of water molecules in the QM region to obtain converged values for this energy term, contrary to most cluster models often employed in the literature. Both the improvement of the QM wave function by means of a larger basis set and the introduction of polarization into the MM region through a polarizable force field do not translate to a faster convergence with the QM region size, but they lead to better results for the different interaction energy components. The results obtained in this work provide insight into the effect of each energy component on the convergence of the solute-solvent interaction energy with the QM region size. This information can be used to improve the MM FFs and embedding schemes employed in QM/MM calculations of solvated systems.

Concentration and solvent effects on structural and thermodynamic properties of uranium (Ⅳ) fluoride by molecular dynamic simulation

The structural and thermodynamic properties of UF4-LiF, UF4-NaF and UF4-KF molten salts were systematically investigated by using molecular dynamic simulation with a polarizable force field, and the effects of UF4 concentration and solvent were discussed. The reliability of molecular dynamic simulation was verified by the reasonable agreements between the calculated and experimental density values of the molten salts. The calculated diffusion coefficients of U4+, Li+, Na+, K+ and F‒ in various systems all followed the form of Arrhenius equation. A linear relationship between the logarithm of viscosity and the reciprocal of temperature was observed. The association between U4+ and F‒ in UF4-KF was strongest, followed by UF4-NaF and UF4-LiF. A transition percentage of 0.3–0.4 for UF4 in mix salts should be paid attention to, which is generally used in nuclear fuel design. The enthalpy of mixing, diffusion coefficient, the radial distribution function and coordination number all showed some transition behaviors at such UF4 transition percentage.

Treating Polarization Effects in Charged and Polar Bio-Molecules Through Variable Electrostatic Parameters.

Polarization plays important roles in charged and hydrogen bonding containing systems. Much effort ranging from the construction of physics-based models to quantum mechanism (QM)-based and machine learning (ML)-assisted models have been devoted to incorporating the polarization effect into the conventional force fields at different levels, such as atomic and coarse grained (CG). The application of polarizable force fields or polarization models was limited by two aspects, namely, computational cost and transferability. Different from physics-based models, no predetermining parameters were required in the QM-based approaches. Taking advantage of both the accuracy of QM calculations and efficiency of molecular mechanism (MM) and ML, polarization effects could be treated more efficiently while maintaining the QM accuracy. The computational cost could be reduced with variable electrostatic parameters, such as the charge, dipole, and electronic dielectric constant with the help of linear scaling fragmentation-based QM calculations and ML models. Polarization and entropy effects on the prediction of partition coefficient of druglike molecules are demonstrated by using both explicit or implicit all-atom molecular dynamics simulations and machine learning-assisted models. Directions and challenges for future development are also envisioned.

Mechanistic understanding of the correlation between structure and dynamics of liquid carbonate electrolytes: impact of polarization.

Liquid electrolyte design and modelling is an essential part of the development of improved lithium ion batteries. For mixed organic carbonates (ethylene carbonate (EC) and ethyl-methyl carbonate (EMC) mixtures)-based electrolytes with LiPF6 as salt, we have compared a polarizable force field with the standard non-polarizable force field with and without charge rescaling to model the structural and dynamic properties. The result of our molecular dynamics simulations shows that both polarizable and non-polarizable force fields have similar structural factors, which are also in agreement with X-ray diffraction experimental results. In contrast, structural differences are observed for the lithium neighborhood, while the lithium-anion neighbourhood is much more pronounced for the polarizable force field. Comparison of EC/EMC coordination statistics with Fourier transformed infrared spectroscopy (FTIR) shows the best agreement for the polarizable force field. Also for transport quantities such as ionic conductivities, transference numbers, and viscosities, the agreement with the polarizable force field is by far better for a large range of salt concentrations and EC : EMC ratios. In contrast, for the non-polarizable variants, the dynamics are largely underestimated. The excellent performance of the polarizable force field is explored in different ways to pave the way to a realistic description of the structure-dynamics relationships for a wide range of salt and solvent compositions for this standard electrolyte. In particular, we can characterize the distinct correlation terms between like and unlike ions, relate them to structural properties, and explore to which degree the transport in this electrolyte is mass or charge limited.

Topology induced crossover between Langevin, subdiffusion, and Brownian diffusion regimes in supercooled water.

Despite extensive studies of supercooled water, it remains challenging to understand its peculiar dynamic anomalous properties. In this work, we integrated full atomistic simulations of supercooled water over the temperature range of room temperature to 200 K using a quantum-mechanics-based polarizable force field with the dressed dynamics method that couples fast collision events and slow reorganization dynamics of hydrogen-bond networks. Our analysis unveils the salient multiscale features in the transient relaxation dynamics of supercooled water. A classical Langevin behavior dominates at fast timescales, while long-time relaxations unveil two different activation barriers in two temperature regions: below and above 230 K. The modulation of the entropy spectrum by temperature is elucidated in terms of a three-state model underlined by the complexity of the water dynamics associated with a topological transition of a strong hydrogen-bond network. This state-dependent network topology is quantitatively characterized by power-law exponents of inverse network connectivity from 200 to 298 K. This work provides valuable guidance for further studies on the transient relaxation dynamics of supercooled water.

Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields.

D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. Structural components often consist of D-Manp residues joined via α-(1→2)-, α-(1→3)-, α-(1→4)- or α-(1→6)-linkages. As models for these oligo- and polysaccharides, a series of mannose-containing disaccharides have been investigated with respect to conformation and dynamics. Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. To attain further spectroscopic data, the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe was synthesized thereby facilitating conformational analysis based on 13C,13C coupling constants as interpreted by Karplus-type relationships. Molecular dynamics simulations were carried out for the disaccharides with explicit water as solvent using the additive CHARMM36 and Drude polarizable force fields for carbohydrates, where the latter showed broader population distributions. Both simulations sampled conformational space in such a way that inter-glycosidic proton-proton distances were very well described whereas in some cases deviations were observed between calculated conformationally dependent NMR scalar coupling constants and those determined from experiment, with closely similar root-mean-square differences for the two force fields. However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates.

Force field refinement for reproducing experimental infrared spectra of ionic liquids.

We employ polarizable molecular dynamics simulations with the newly developed FFGenOpt parametrization tool to reproduce IR spectra of several ionic liquid cations and anions in the gas phase. Our results show that polarizable force fields in the bulk phase provide a reasonable compromise between computational effort and accuracy for investigating IR spectra when treating the transition from gas to liquid phase carefully. Although collectivity seems to play only a minor role, the liquid phase not only changes the electrostatic environment of the molecules but also introduces friction and intermolecular interactions altering the IR spectrum significantly. In addition to the classical force field approach, we also tested if the additional computational effort of machine learning potentials justifies their application in reproducing IR spectra. However, the main purpose of this work is to improve the quality of polarizable force fields concerning vibrations and not the prediction of IR spectra which can be better done with quantum-mechanical cluster approaches.

Limitations of non-polarizable force fields in describing anion binding poses in non-polar synthetic hosts.

Transmembrane anion transport by synthetic ionophores has received increasing interest not only because of its relevance for understanding endogenous anion transport, but also because of potential implications for therapeutic routes in disease states where chloride transport is impaired. Computational studies can shed light on the binding recognition process and can deepen our mechanistic understanding of them. However, the ability of molecular mechanics methods to properly capture solvation and binding properties of anions is known to be challenging. Consequently, polarizable models have been suggested to improve the accuracy of such calculations. In this study, we calculate binding free energies for different anions to the synthetic ionophore, biotin[6]uril hexamethyl ester in acetonitrile and to biotin[6]uril hexaacid in water by employing non-polarizable and polarizable force fields. Anion binding shows strong solvent dependency consistent with experimental studies. In water, the binding strengths are iodide > bromide > chloride, and reversed in acetonitrile. These trends are well captured by both classes of force fields. However, the free energy profiles obtained from potential of mean force calculations and preferred binding positions of anions depend on the treatment of electrostatics. Results from simulations using the AMOEBA force-field, which recapitulate the observed binding positions, suggest strong effects from multipoles dominate with a smaller contribution from polarization. The oxidation status of the macrocycle was also found to influence anion recognition in water. Overall, these results have implications for the understanding of anion host interactions not just in synthetic ionophores, but also in narrow cavities of biological ion channels.

Development of a QM/MM(ABEEM) method combined with a polarizable force field to investigate the excision reaction mechanism of damaged thymine.

This paper focuses on the development of a quantum mechanics/molecular mechanics method using the ABEEM polarizable force field (QM/MM(ABEEM) method) to investigate the excision reaction mechanism of damaged thymine. This method does not simply combine the QM method with the polarizable force field. A valence electronegativity piecewise function with the distance between atoms as a variable is introduced to describe the atomic partial charges, and changes greatly during the reaction process. At the same time, the charge transfer effect is treated using the condition of local charge conservation. Compared with the traditional QM/MM method, the QM/MM(ABEEM) method can more accurately simulate the polarization effect and charge transfer effect in the reaction process. Focusing on the controversial problems of the excision of damaged bases, six reaction pathways were designed for monofunctional and difunctional deglycosylation of neutral bases and protonated bases. The results show that the QM/MM(ABEEM) method accurately simulates the polarization effect, charge transfer effect, activation energy and other properties of the reaction process. The process in which the active residue Asp activates the nucleophile H2O to attack the protonated base is the preferred path. The average activation energy and free activation energy of the protonated base are 7.00-14.00 kcal mol-1 lower than that of the neutral base. The study in this paper is helpful to understand the mechanism of repair enzymes in repairing bases.

Structure and self-diffusivity of alkali-halide electrolytes in neutral and charged graphene nanochannels.

Understanding the microscopic behaviour of aqueous electrolyte solutions in graphene-based ultrathin nanochannels is important in nanofluidic applications such as water purification, fuel cells, and molecular sensing. Under extreme confinement (<2 nm), the properties of water and ions differ drastically from those in the bulk phase. We studied the structural and diffusion behaviour of prototypical aqueous solutions of electrolytes (LiCl, NaCl, and KCl) confined in both neutral and positively-, and negatively-charged graphene nanochannels. We performed molecular dynamics simulations of the solutions in the nanochannels with either one, two- or three-layer water structures using the effectively polarisable force field for graphene. We analysed the structure and intermolecular bond network of the confined solutions along with their relation to the self-diffusivity of water and ions. The simulations show that Na and K cations can more easily rearrange their solvation shells under the graphene nanoconfinement and adsorb on the graphene surfaces or dissolve in the confinement-induced layered water than the Li cation. The negative surface charge together with the presence of ions orient water molecules with hydrogens towards the graphene surfaces, which in turn weakens the intermolecular bond network. The one-layer nanochannels have the biggest effect on the water structure and intermolecular bonding as well as on the adsorption of ions with only co-ions entering these nanochannels. The self-diffusivity of confined water is strongly reduced with respect to the bulk water and decreases with diminishing nanochannel heights except for the negatively-charged one-layer nanochannel. The self-diffusivity of ions also decreases with the reducing the nanochannel heights except for the self-diffusivity of cations in the negatively-charged one-layer nanochannel, evidencing cooperative diffusion of confined water and ions. Due to the significant break-up of the intermolecular bond network in the negatively-charged one-layer nanochannel, self-diffusion coefficients of water and cations exceed those for the two- and three-layer nanochannels and become comparable to the bulk values.

Capturing charge and size effects of ions at the graphene-electrolyte interface using polarizable force field simulations.

We present a systematic investigation capturing the charge and size effects of ions interacting with a graphene surface using polarizable simulations. Our results utilizing the Drude polarizable force field (FF) for ions, water and graphene surfaces, show that the graphene parameters previously developed by us are able to accurately capture the dynamics at the electrolyte-graphene interface. For monovalent ions, with increasing size, the solvation shell plays a crucial role in controlling the ion-graphene interactions. Smaller monovalent ions directly interact with the graphene surface, while larger ions interact with the graphene surface via a well-formed solvation shell. For divalent ions, both interaction modes are observed. For the anion Cl-, we observe direct interaction between the ions and the graphene surface. The anion-graphene interactions are strongly driven by the polarizability of the graphene surface. These effects are not captured in the absence of polarization by additive FF simulations. The present study underlines the importance of polarizability in capturing the interfacial phenomenon at the solid-solute interface.

Breakdown of the Nernst-Einstein relation in carbon nanotube porins.

For over 100 years, the Nernst-Einstein relation has linked a charged particle's electrophoretic mobility and diffusion coefficient. Here we report experimental measurements of diffusion and electromigration of K+ ions in narrow 0.8-nm-diameter single-walled carbon nanotube porins (CNTPs) and demonstrate that the Nernst-Einstein relation in these channels breaks down by more than three orders of magnitude. Molecular dynamics simulations using polarizable force fields show that K+ ion diffusion in CNTPs in the presence of a single-file water chain is three orders of magnitude slower than bulk diffusion. Intriguingly, the simulations also reveal a disintegration of the water chain upon application of electric fields, resulting in the formation of distinct K+-water clusters, which then traverse the CNTP at high velocity. Finally, we show that although individual ion-water clusters still obey the Nernst-Einstein relation, the overall relation breaks down because of two distinct mechanisms for ion diffusion and electromigration.

Characterizing Ion-Polymer Interactions in Aqueous Environment with Electric Fields.

Polymers make the basis of highly tunable materials that could be designed and optimized for metal recovery from aqueous environments. While experimental studies show that this approach has potential, it suffers from a limited knowledge of the detailed molecular interaction between polymers and target metal ions. Here, we propose to calculate intrinsic electric fields from polarizable force field molecular dynamics simulations to characterize the driving force behind Eu3+ motion in the presence of poly(ethylenimine methylenephosphonate), a specifically designed metal chelating polymer. Focusing on the metal chelation initiation step (i.e., before binding), we can rationalize the role of each molecule on ion dynamics by projecting these electric fields along the direction of ion motion. We find that the polymer functional groups act indirectly, and the polymer-metal ion interaction is actually mediated by water. This result is consistent with the experimental observation that metal sequestration by these polymers is entropically driven. This study suggests that electric field calculations can help the design of metal chelating polymers, for example, by seeking to optimize polymer-solvent interactions rather than polymer-ion interactions.

Δ-Machine Learned Potential Energy Surfaces and Force Fields

There has been great progress in developing machine-learned potential energy surfaces (PESs) for molecules and clusters with more than 10 atoms. Unfortunately, this number of atoms generally limits the level of electronic structure theory to less than the "gold standard" CCSD(T) level. Indeed, for the well-known MD17 dataset for molecules with 9-20 atoms, all of the energies and forces were obtained with DFT calculations (PBE). This Perspective is focused on a Δ-machine learning method that we recently proposed and applied to bring DFT-based PESs to close to CCSD(T) accuracy. This is demonstrated for hydronium, N-methylacetamide, acetyl acetone, and ethanol. For 15-atom tropolone, it appears that special approaches (e.g., molecular tailoring, local CCSD(T)) are needed to obtain the CCSD(T) energies. A new aspect of this approach is the extension of Δ-machine learning to force fields. The approach is based on many-body corrections to polarizable force field potentials. This is examined in detail using the TTM2.1 water potential. The corrections make use of our recent CCSD(T) datasets for 2-b, 3-b, and 4-b interactions for water. These datasets were used to develop a new fully ab initio potential for water, termed q-AQUA.

Polarizable Molecular Block Model: Toward the Development of an Induced Dipole Force Field for DNA.

For flexible and highly ionized macromolecules such as DNA, it is important to correctly evaluate the intramolecular polarization in an induced dipole force field. In a proposed polarizable molecular block (PMB) model, a large molecule is divided into several molecular blocks. The atomic charges of the blocks are optimized by using the respective electrostatic potentials (ESPs) on the molecular surface. By using the capped hydrogen removal operation, the total charge of the blocks is controlled exactly to have an integer charge. The atomic polarizabilities of the blocks are optimized by using the respective polarized one-electron potentials that are the differences between ESPs with and without an external test charge. Induced dipole-charge interactions between the blocks are all included, but those interactions within the blocks are strictly excluded. All dipole-dipole interactions are included, but the damping functions are applied to the close dipole-dipole pairs. Several types of damping (simple scaling, exponential, linear, and Gaussian) are evaluated. The validity of the PMB model was verified by using trinucleotide duplexes which have A-, B-, and Z-DNA forms. The reference energies of trinucleotide duplexes including counterions (GGT3Na-ACC3Na, GAC3Na-GTC3Na, and GCG3Na-CGC3Na) are calculated using ωB97XD/aug-cc-pVDZ. All damping types reproduced well the reference interaction energies, dipole moments, and ESPs. Among them, the simple scaling with strong attenuation to 1-2 atomic pairs showed the highest stability against the polarization catastrophe. This study shows that it is possible to develop a high-quality polarizable force field by treating the intramolecular polarization on a block-by-block basis.

Molecular Dynamics and Free Energy Calculations of Dicyclohexano-18-crown-6 Diastereoisomers with Sm2+, Eu2+, Dy2+, Yb2+, Cf2+, and Three Halide Salts in Tetrahydrofuran and Acetonitrile Using the AMOEBA Force Field.

With the continual development of lanthanides (Ln) in current technological devices, an efficient separation process is needed that can recover greater amounts of these rare elements. Dicyclohexano-18-crown-6 (DCH18C6) is a crown ether that may be a promising candidate for Ln separation, but additional research is required. As such, molecular dynamics (MD) simulations have been performed on four divalent lanthanide halide salts (Sm2+, Eu2+, Dy2+, and Yb2+) and one divalent actinide halide salt (Cf2+) bound to three diastereoisomers of DCH18C6. Dy2+, Yb2+, Cf2+, DCH18C6, and tetrahydrofuran (THF) solvent were parameterized for the AMOEBA polarizable force field for the first time, whereas existing parameters for Sm2+ and Eu2+ were utilized from our previous efforts. A coordination number (CN) of six for Ln2+/An2+-O solvated in THF indicated that the cations interacted almost entirely with the oxygens of the polyether ring. A CN of one for Ln2+/An2+-N solvated in acetonitrile for systems containing iodide suggested that the N atom of acetonitrile was competitive with I- for cation interactions. Fluctuation between five and six CNs for Dy2+ and Yb2+ suggested that although the cations remained in the polyether ring, the size of the ring may not be an ideal fit as these cations possess comparatively smaller ionic radii. Gibbs binding free energies of Sm2+ in all DCH18C6 diastereoisomers solvated in THF were calculated. The binding free energy of the cis-syn-cis diastereoisomer was the most favorable, followed by cis-anti-cis, and then trans-anti-trans. Finally, two major types of conformation were observed for each diastereoisomer that were related to the electrostatic interactions and charge density of the cations.

Impact of Polarization on the Ring Puckering Dynamics of Hexose Monosaccharides.

Analysis of crystal structures of hexose monosaccharides α-d-mannose (α-MAN), β-d-mannose (β-MAN), α-d-glucose (α-GLC), β-d-glucose (β-GLC), α-d-galactose (α-GAL), β-d-galactose (β-GAL), α-d-altrose (α-ALT), β-d-altrose (β-ALT), α-d-idose (α-IDO), and β-d-idose (β-IDO) reveals that the monosaccharide ring adopts multiple ring conformations. These ring conformations can be broadly classified as chair, half-chair, envelope, boat, and skew-boat conformations. The ability of the monosaccharide ring to adopt multiple conformations has been closely tied with their bioactivity. However, it has been difficult to capture the dynamic information of these conformations from experimental studies. Even from simulations, capturing these different conformations is challenging because of the energy barriers involved in the transitions between the stable 4C1 and 1C4 chair forms. In this study, we analyze the influence of the polarizable force field on the ring dynamics of five major types of unsubstituted aldohexoses─glucose, mannose, galactose, altrose, and idose─and their anomers. We simulate microsecond trajectories to capture the influence of the CHARMM36 additive and polarizable carbohydrate force fields on the ring dynamics. The microsecond trajectories allow us to comment on the issues associated with equilibrium molecular dynamics simulations. Further, we use the extended system adaptive biasing force (eABF) method to compare the conformational sampling efficiencies of the additive and polarizable force fields. Our studies reveal that inclusion of polarization enhances the sampling of ring conformations and lowers the energy barriers between the 4C1 and 1C4 conformations. Overall, the CHARMM36 additive force field is observed to be rigid and favor the 4C1 conformations. Although the inclusion of polarizability results in enhancing ring flexibility, we observe sampling that does not agree with experimental results, warranting a revision of the polarizable Drude parameters.

Extending the applicability of popular force fields for describing water/metal interfaces: application to water/Pd(111)

We propose a new method for constructing a polarizable classical force field using data obtained from QM and QM/MM calculations to account for the charge redistribution at the water/metal interface. The induced charge effects are described by adding dipoles to the system topology following the Rod Model (Iori, F, et al J. Comput. Chem.2009, 30, 1465). Furthermore, the force field uses the TIP3P water model, and its functional form is compatible with popular force fields such as AMBER, CHARMM, GROMOS, OPLS-AA, CVFF and IFF. The proposed model was evaluated and validated for water/Pd(111) systems. We tuned the model parameters to reproduce a few critical water/Pd(111) geometries and energies obtained from DFT calculations using both PBE and a non-local van der Waals xc-functional. Our model can reproduce the hexagonal ice layer for the Pd(111)/water systems typically present in low-temperature experiments, in agreement with information available from the literature. Additionally, the model can also reproduce the experimental metal-water interfacial tension at room temperature.

Protein-Ligand Binding Free-Energy Calculations with ARROW─A Purely First-Principles Parameterized Polarizable Force Field.

Protein-ligand binding free-energy calculations using molecular dynamics (MD) simulations have emerged as a powerful tool for in silico drug design. Here, we present results obtained with the ARROW force field (FF)─a multipolar polarizable and physics-based model with all parameters fitted entirely to high-level ab initio quantum mechanical (QM) calculations. ARROW has already proven its ability to determine solvation free energy of arbitrary neutral compounds with unprecedented accuracy. The ARROW FF parameterization is now extended to include coverage of all amino acids including charged groups, allowing molecular simulations of a series of protein-ligand systems and prediction of their relative binding free energies. We ensure adequate sampling by applying a novel technique that is based on coupling the Hamiltonian Replica exchange (HREX) with a conformation reservoir generated via potential softening and nonequilibrium MD. ARROW provides predictions with near chemical accuracy (mean absolute error of ∼0.5 kcal/mol) for two of the three protein systems studied here (MCL1 and Thrombin). The third protein system (CDK2) reveals the difficulty in accurately describing dimer interaction energies involving polar and charged species. Overall, for all of the three protein systems studied here, ARROW FF predicts relative binding free energies of ligands with a similar accuracy level as leading nonpolarizable force fields.

Molecular dynamic study of the local structure and transport properties of LiF-NaF molten salt

LiF-NaF molten salts have received extensive attention due to their excellent heat transfer performance in molten salt reactors. However, their structural and thermodynamic properties have not been systematically studied. In this study, molecular dynamic simulations were performed using polarized force fields to investigate the local structures of cations and thermodynamic properties of mixed salts in a temperature range of 873 K to 1273 K and at all concentration components. Furthermore, a linear relationship between density and LiF concentration at different temperatures was fitted. Regarding local structure, an increase in LiF concentration gradually increased the coordination numbers of Li and Na ions, but the strength of Li–F and Na–F ionic bonds gradually weakened. Regarding the thermodynamic properties, an increase in the LiF concentration linearly increased the self-diffusion coefficients of all ionic species, while the viscosity of the system approximately decreases exponentially. The ionic conductivities were calculated using the Green–Kubo and Nernst–Einstein relationships, and the results reflect that the Nernst–Einstein approximation is not suitable for describing molten salt systems.