Force Field Parametrization from the Hirshfeld Molecular Electronic Density

Abstract

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.

Improved description of ligand polarization enhances transferability of ion–ligand interactions

“…We note that the recommended strategy to calibrate force fields is to include certain condensed phase properties as optimization targets. 49,50 Here, we are not including them as targets because we want to examine how improving local interactions affects predictions of condensed phase properties.…”

Systematic optimization of a fragment-based force field against experimental pure-liquid properties considering large compound families: application to oxygen and nitrogen compounds

“…In hybrid force fields 14,15 (HYFF), the covalent and van der Waals parameters are selected in a FBFF fashion, but the partial charges are derived based on quantummechanics (QM) calculations involving the target molecule in a given environment (implicit solvent), typically via electrostatic-potential fitting [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] or electron-density partitioning. [29][30][31][32][33][34][35][36][37][38] The assumption invoked is that of a separability between van der Waals coefficients and partial charges. Given a selected charge-derivation scheme, the van der Waals parameters are again calibrated primarily against experimental condensed-phase data for small compounds.…”

“…they result from ad hoc derivation recipes rather than physics-based rules, and their values may also strongly depend on the choice of a QM level of theory and basis set; [21][22][23][24][25][69][70][71][72][73][74][75] (iii) in practice, some parameters must still be optimized empirically, 21,26,27,40,46,74,75 e.g. van der Waals coefficients in HYFF and van der Waals repulsion coefficients 38,44,45,56,57,76,77 in QDFF.…”

“…hardness and electronegativity, are expected to factor out these induction effects and be much less dependent than the partial charges themselves on the covalent environment of the atoms. Note that although the EE scheme serves to generate atomic partial charges, its function is fundamentally distinct from the electrostatic-potential fitting [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] or electron-density partitioning [29][30][31][32][33][34][35][36][37][38] procedures used in HYFF and QDFF force fields. Whereas the latter procedures aim at deriving partial charges based on a QM calculation, the EE scheme is only used as a physically-motivated parametricfitting device for the electrostatic interactions in the liquid, where the partial charges are solely determined by the condensed-phase properties (no QM input).…”

Structural and Energetic Affinity of Annocatacin B with ND1 Subunit of the Human Mitochondrial Respiratory Complex I as a Potential Inhibitor: An In Silico Comparison Study with the Known Inhibitor Rotenone

“…With these charges, and using the OPLS/AA parameters, we built the annocatacin B and rotenone force fields for the MD simulations. Hirshfeld’s atomic charges calculation and their use in molecular mechanics (MM) force fields has been employed in many liquid solvents studies [ 63 , 64 , 65 , 66 , 67 ]. The main advantages of these atomic charges are not to overestimate the electrostatic properties and accelerate the MD calculations.…”