Evaluation of CM5 Charges for Nonaqueous Condensed-Phase Modeling

Abstract

Partial atomic charges for neutral molecules from quantum mechanical calculations are typically scaled for use in molecular modeling of liquid-phase systems. Optimal scale factors of 1.14 for CM1A and 1.27 for CM5 charges were previously determined for minimizing errors in free energies of hydration. The adequacy of the 1.14*CM1A and 1.27*CM5 models are evaluated here in pure liquid simulations in combination with the OPLS-AA force field. For 22 organic liquids, the 1.14*CM1A and 1.27*CM5 models yield mean unsigned errors (MUEs) of ca. 1.40 kcal/mol for heats of vaporization. Not surprisingly, this reflects overpolarization with the scale factors derived for aqueous media. Prediction of pure liquid properties using CM5 charges is optimized using a scale factor of 1.14, which reduces the MUE for heats of vaporization to 0.89 kcal/mol. However, due to the impracticality of using different scale factors in different explicit-solvent condensed-phase simulations, a universal scale factor of 1.20 emerged for CM5 charges. This provides a balance between errors in computed pure liquid properties and free energies of hydration. Computation of free energies of hydration by the GB/SA method further found that 1.20 is equally suited for use in explicit or implicit treatments of aqueous solvation. With 1.20*CM5 charges, a variety of condensed-phase simulations can be pursued while maintaining average errors of 1.0 kcal/mol in key thermodynamic properties.

1.14*CM1A-LBCC: Localized Bond-Charge Corrected CM1A Charges for Condensed-Phase Simulations

“…In addition, it makes computed ΔG hyd values too positive with a Mean Signed Deviation (MSD; experiment - calculated) of −1.14 kcal/mol; however, use of a larger scale factor with CM5 would lead to poorer results for liquid densities and heats of vaporization. 29,30 The other advantage of correcting the CM1A rather than CM5 charges is the relative simplicity of the underlying AM1 calculations for the former.…”

“…It was found that use of only 19 LBCC was able to lower the MAD for the 426 free energies of hydration to 0.61 kcal/mol. Further improvements are expected to be limited by the accuracy of the experimental data 30 and the simplicity of the atom-centered point charge model. The 1.14*CM1A-LBCC charges in conjunction with the OPLS-AA force field were also tested for calculating heats of vaporization ( ΔH vap ) and densities of ca.…”

“…100 liquids with OPLS-AA, for which the parameterization has emphasized this property and liquid densities. 3,30 The 1.14*CM1A-based charge models on average over-estimate heats of vaporization by ca. 1 kcal/mol as shown by the MSDs, although the values for the MADs are essentially unchanged.…”

Predicting water-to-cyclohexane partitioning of the SAMPL5 molecules using dielectric balancing of force fields

“…This modulation involves a 20 % magnification of the AM1-BCC partial charges and a corresponding linear inflation of the Lennard–Jones parameters to maintain the proper liquid densities with the increased charge magnitudes. This degree of charge magnitude amplification has been seen as beneficial for neat liquid and molecular transfer properties by our group and others [15, 25], while the linear inflation is derived from automated dielectric optimization of small molecule functional groups. Here, the modulation amounts to a generally applied percent inflation for each atom of the molecule.…”

Hydration Properties and Solvent Effects for All-Atom Solutes in Polarizable Coarse-Grained Water

“…$$H_{\mathrm{italictot}}=H_{int\mathit{ra}}^{AA}+H_{int\mathit{er}}^{AA}+H_{int\mathit{ra}}^{CG}+H_{int\mathit{er}}^{CG}+H_{int\mathit{er}}^{CG/AA}.$$ parameters of the OPLS-AA force field 25,26 with 1.14*CM1A 31,32 or 1.20*CM5 28,33,34 partial atomic charges were used to describe solute interactions. Martini force field 2.0 35 and the polarizable Martini CG water model 27 were used for intra- and inter-molecular CG interactions.…”