Polarizable molecular interactions in condensed phase and their equivalent nonpolarizable models

Atomistic molecular simulations are a powerful way to make quantitative predictions, but the accuracy of these predictions depends entirely on the quality of the forcefield employed. While experimental measurements of fundamental physical properties offer a straightforward approach for evaluating forcefield quality, the bulk of this information has been tied up in formats that are not machine-readable. Compiling benchmark datasets of physical properties from non-machine-readable sources requires substantial human effort and is prone to the accumulation of human errors, hindering the development of reproducible benchmarks of forcefield accuracy. Here, we examine the feasibility of benchmarking atomistic forcefields against the NIST ThermoML data archive of physicochemical measurements, which aggregates thousands of experimental measurements in a portable, machine-readable, self-annotating IUPAC-standard format. As a proof of concept, we present a detailed benchmark of the generalized Amber small molecule forcefield (GAFF) using the AM1-BCC charge model against experimental measurements (specifically bulk liquid densities and static dielectric constants at ambient pressure) automatically extracted from the archive, and discuss the extent of data available for use in larger scale (or continuously performed) benchmarks. The results of even this limited initial benchmark highlight a general problem with fixed-charge forcefields in the representation low dielectric environments such as those seen in binding cavities or biological membranes.

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“…15,49 However, a number of authors have pointed out potential challenges in constructing self-consistent fixed-charge forcefields. 50,51 …”

Section: Discussionmentioning

confidence: 99%

Toward Automated Benchmarking of Atomistic Force Fields: Neat Liquid Densities and Static Dielectric Constants from the ThermoML Data Archive

Beauchamp

Behr²,

Rustenburg³

et al. 2015

J. Phys. Chem. B

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“…Refs. [43,[91][92][93][94][95] and references therein). A water model dependent but ionic model independent charge rescaling method was proposed recently in Ref.…”

Section: Self-diffusion Coefficientsmentioning

confidence: 99%

A comparison of classical interatomic potentials applied to highly concentrated aqueous lithium chloride solutions

Pethes

2017

Journal of Molecular Liquids

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Aqueous lithium chloride solutions up to very high concentrations were investigated in classical molecular dynamics simulations. Various force fields based on the 12-6 Lennard-Jones model, parametrized for non-polarizable water solvent molecules (SPC/E, TIP4P, TIP4PEw), were inspected.Twenty-nine combinations of ion-water interaction models were examined at four different salt concentrations. Densities, static dielectric constants and self-diffusion coefficients were calculated.Results derived from the different force fields scatter over a wide range of values. Neutron and X-ray weighted structure factors were also calculated from the radial distribution functions and compared with experimental data. It was found that the agreement between calculated and experimental curves is rather poor for several investigated potential models, even though some of them have previously been applied in computer simulations.None of the investigated models yield satisfactory results for all the tested quantities. Only two parameter sets provide acceptable predictions for the structure of highly concentrated aqueous LiCl solutions. Some approaches for adjusting potential parameters, such as those of Aragones [Aragones et al., J. Phys. Chem. B 118 (2014) 7680] and Pluharova [Pluharova et al, J. Phys. Chem. A 117 (2013) 11766], were tested as well; the simulations presented here underline their usefulness. These refining methods are suited to obtain more appropriate ion/water potentials.

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“…Recently, several ion models have augmented this “12‐6” potential with an additional

r^{- 4}

term, giving rise to a “12‐6‐4” potential that provides some improvement . Finally, another potentially useful approach for accounting for electronic polarization in nonpolarizable models is to scale partial charges by the inverse of the square root of the dielectric constant of the medium . Although no such models exist to date for magnesium ions, parameters for calcium and monovalents like lithium and potassium have been developed.…”

Section: Introductionmentioning

confidence: 99%

Comparison of structural, thermodynamic, kinetic and mass transport properties of Mg²⁺ ion models commonly used in biomolecular simulations

2015

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The prevalence of Mg2+ ions in biology and their essential role in nucleic acid structure and function has motivated the development of various Mg2+ ion models for use in molecular simulations. Currently the most widely used models in biomolecular simulations represent a non-bonded metal ion as an ion-centered point charge surrounded by a non-electrostatic pairwise potential that takes into account dispersion interactions and exchange effects that give rise to the ion's excluded volume. One strategy toward developing improved models for biomolecular simulations is to first identify a Mg2+ model that is consistent with the simulation force fields that closely reproduces a range of properties in aqueous solution, and then, in a second step, balance the ion-water and ion-solute interactions by tuning parameters in a pairwise fashion where necessary. The present work addresses the first step in which we compare 17 different non-bonded single-site Mg2+ ion models with respect to their ability to simultaneously reproduce structural, thermodynamic, kinetic and mass transport properties in aqueous solution. None of the models based on a 12-6 non-electrostatic non-bonded potential was able to reproduce the experimental radial distribution function, solvation free energy, exchange barrier and diffusion constant. The models based on a 12-6-4 potential offered improvement, and one model in particular, in conjunction with the SPC/E water model, performed exceptionally well for all properties. The results reported here establish useful benchmark calculations for Mg2+ ion models that provide insight into the origin of the behavior in aqueous solution, and may aid in the development of next-generation models that target specific binding sites in biomolecules.

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Polarizable molecular interactions in condensed phase and their equivalent nonpolarizable models

Cited by 86 publications

References 76 publications

Toward Automated Benchmarking of Atomistic Force Fields: Neat Liquid Densities and Static Dielectric Constants from the ThermoML Data Archive

Toward Automated Benchmarking of Atomistic Force Fields: Neat Liquid Densities and Static Dielectric Constants from the ThermoML Data Archive

A comparison of classical interatomic potentials applied to highly concentrated aqueous lithium chloride solutions

Comparison of structural, thermodynamic, kinetic and mass transport properties of Mg²⁺ ion models commonly used in biomolecular simulations

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Polarizable molecular interactions in condensed phase and their equivalent nonpolarizable models

Cited by 86 publications

References 76 publications

Toward Automated Benchmarking of Atomistic Force Fields: Neat Liquid Densities and Static Dielectric Constants from the ThermoML Data Archive

Toward Automated Benchmarking of Atomistic Force Fields: Neat Liquid Densities and Static Dielectric Constants from the ThermoML Data Archive

A comparison of classical interatomic potentials applied to highly concentrated aqueous lithium chloride solutions

Comparison of structural, thermodynamic, kinetic and mass transport properties of Mg2+ ion models commonly used in biomolecular simulations

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Product

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Comparison of structural, thermodynamic, kinetic and mass transport properties of Mg²⁺ ion models commonly used in biomolecular simulations