Evaluation of CM5 Charges for Nonaqueous Condensed-Phase Modeling.

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 1.14CM1A and 1.27CM5 models are evaluated here in pure liquid simulations in combination with the OPLS-AA force field. For 22 organic liquids, the 1.14CM1A and 1.27CM5 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.