Polarizable Force Field with a σ-Hole for Liquid and Aqueous Bromomethane

London dispersion interactions play an integral role in materials science and biophysics. Force fields for atomistic molecular simulations typically represent dispersion interactions by the 12-6 Lennard-Jones potential using empirically determined parameters. These parameters are generally underdetermined, and there is no straightforward way to test if they are physically realistic. Alternatively, the exchange-hole dipole moment (XDM) model from density-functional theory predicts atomic and molecular London dispersion coefficients from first principles, providing an innovative strategy to validate the dispersion terms of molecular-mechanical force fields. In this work, the XDM model was used to obtain the London dispersion coefficients of 88 organic molecules relevant to biochemistry and pharmaceutical chemistry and the values compared with those derived from the Lennard-Jones parameters of the CGenFF, GAFF, OPLS, and Drude polarizable force fields. The molecular dispersion coefficients for the CGenFF, GAFF, and OPLS models are systematically higher than the XDM-calculated values by a factor of roughly 1.5, likely due to neglect of higher order dispersion terms and premature truncation of the dispersion-energy summation. The XDM dispersion coefficients span a large range for some molecular-mechanical atom types, suggesting an unrecognized source of error in force-field models, which assume that atoms of the same type have the same dispersion interactions. Agreement with the XDM dispersion coefficients is even poorer for the Drude polarizable force field. Popular water models were also examined, and TIP3P was found to have dispersion coefficients similar to the experimental and XDM references, although other models employ anomalously high values. Finally, XDM-derived dispersion coefficients were used to parametrize molecular-mechanical force fields for five liquids-benzene, toluene, cyclohexane, n-pentane, and n-hexane-which resulted in improved accuracy in the computed enthalpies of vaporization despite only having to evaluate a much smaller section of the parameter space.

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“…Adluri et al showed that the GAFF model for bromomethane could be improved by reparameterizing the Lennard-Jones terms for Br. 55…”

Section: Halogensmentioning

confidence: 99%

Evaluating Force-Field London Dispersion Coefficients Using the Exchange-Hole Dipole Moment Model

Mohebifar

Johnson

Rowley

2017

J. Chem. Theory Comput.

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“…The Lennard-Jones parameters are typically assigned empirically such that simulations using these parameters accurately predict the properties of representative bulk liquids (e.g., density, enthalpy of vaporization, dielectric constant, etc. ), 10,[12][13][14][15][16][17] although some QM-based approaches have also been applied. [18][19][20][21][22] A drawback of parameterizing Lennard-Jones parameters empirically is that they are generally underdetermined when molecules contain multiple types of atoms, allowing widely different parameters to be defined for them.…”

Section: Introductionmentioning

confidence: 99%

Evaluating the London Dispersion Coefficients of Protein Force Fields Using the Exchange-Hole Dipole Moment Model

et al. 2018

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London dispersion is one of the fundamental interactions involved in protein folding and dynamics. The popular CHARMM36, Amber ff14sb, and OPLS-AA force fields represent these interactions through the C/ r term of the Lennard-Jones potential, where the C parameters are assigned empirically. Here, dispersion coefficients of these three force fields are shown to be roughly 50% larger than values calculated using the quantum mechanically derived exchange-hole dipole moment (XDM) model. The CHARMM36 and Amber OL15 force fields for nucleic acids also exhibit this trend. The hydration energies of the side-chain models were calculated using REMD-TI for the CHARMM36, Amber ff14sb, and OPLS-AA force fields. These force fields predict side-chain hydration energies that are in generally good agreement with the experimental values, which suggests that the total strength of aqueous dispersion interactions is correct, despite C coefficients that are considerably larger than XDM predicts. An analytical expression for the dispersion hydration energy using XDM coefficients shows that higher-order dispersion terms (i.e., C and C) account for roughly 37.5% of the hydration energy of methane. This suggests that the C dispersion coefficients used in contemporary force fields are elevated to account for the neglected higher-order terms.

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“…Lennard-Jones parameters for bromine are not optimal. 55 The bromine dispersion coefficients for the reparameterized force field were closer to the XDM values (206.7 a.u. and 163.1 a.u.…”

Section: Molecular Dispersion Coefficientsmentioning

confidence: 53%

Evaluating Force-Field London Dispersion Coefficients Using the Exchange-Hole Dipole Moment Model

Mohebifar¹,

Johnson²,

Rowley³

2017

Preprint

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London dispersion interactions play an integral role in materials science and biophysics. Force fields for atomistic molecular simulations typically represent dispersion interactions by the 12-6 Lennard-Jones potential, using empirically-determined parameters. These parameters are generally underdetermined and there is no straightforward way to test if they are physically realistic. Alternatively, the exchange-hole dipole moment (XDM) model from density-functional theory predicts atomic and molecular London dispersion coefficients from first principles, providing an innovative strategy to validate the dispersion terms of molecular-mechanical force fields. In this work, the XDM model was used to obtain the London dispersion coefficients of 88 organic molecules relevant to biochemistry and pharmaceutical chemistry and the values compared with those derived from the Lennard-Jones parameters of the CGenFF, GAFF, OPLS, and Drude polarizable force fields. The molecular dispersion coefficients for the CGenFF, GAFF, and OPLS models are systematically higher than the XDM-calculated values by a factor of roughly 1.5, likely due to neglect of higher-order dispersion terms and premature truncation of the dispersion-energy summation. The XDM dispersion coefficients span a large range for some molecular-mechanical atom types, suggesting an unrecognized source of error in force-field models, which assume that atoms of the same type have the same dispersion interactions. Agreement with the XDM dispersion coefficients is even poorer for the Drude polarizable force field. Popular water models were also examined and TIP3P was found to have dispersion coefficients similar to the experimental and XDM references, although other models employ anomalously high values. Finally, XDM-derived dispersion coefficients were used to parameterize molecular-mechanical force fields for five liquids -benzene, toluene, cyclohexane, npentane, and n-hexane -which resulted in improved accuracy in the computed enthalpies of vaporization despite only having to evaluate a much smaller section of the parameter space.

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Polarizable Force Field with a σ-Hole for Liquid and Aqueous Bromomethane

Cited by 20 publications

References 90 publications

Evaluating Force-Field London Dispersion Coefficients Using the Exchange-Hole Dipole Moment Model

Evaluating Force-Field London Dispersion Coefficients Using the Exchange-Hole Dipole Moment Model

Evaluating the London Dispersion Coefficients of Protein Force Fields Using the Exchange-Hole Dipole Moment Model

Evaluating Force-Field London Dispersion Coefficients Using the Exchange-Hole Dipole Moment Model

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