Benchmarking Electronic Structure Methods for Accurate Fixed-Charge Electrostatic Models.

Area of Science:

• Computational Chemistry
• Molecular Modeling
• Physical Chemistry

Background:

• Classical molecular mechanics (MM) force fields are crucial for condensed phase simulations.
• Accurate modeling of nonbonded interactions, particularly electrostatics, is vital for MM force field accuracy.
• Popular fixed-charge MM force fields often use partial atomic charges derived from gas-phase Hartree-Fock (HF)/6-31G* calculations.

Purpose of the Study:

• To evaluate the accuracy of HF/6-31G* for deriving partial atomic charges for MM force fields.
• To investigate alternative, computationally inexpensive methods for generating more accurate partial atomic charges.
• To assess the suitability of density functional theory (DFT) methods for next-generation MM force field development.

Main Methods:

• Evaluated HF/6-31G* method/basis set combination using a benchmark set of 47 molecules.
• Compared calculated gas-phase dipole moments with experimental values.
• Investigated computationally inexpensive DFT methods with augmented basis sets and a continuum solvent model.

Main Results:

• HF/6-31G* overpolarizes molecular dipole moments by approximately 10% on average compared to experimental gas-phase values.
• The degree of overpolarization with HF/6-31G* is inconsistent, sometimes resulting in lower dipole moments than experimental.
• DFT methods with appropriate basis sets and solvent models yield more consistently and strongly overpolarized molecular dipole moments.

Conclusions:

• The HF/6-31G* method/basis set is not optimal for deriving partial atomic charges for MM force fields due to inconsistent overpolarization.
• Computationally inexpensive DFT methods offer a promising alternative for generating accurate partial atomic charges.
• Adoption of DFT-based methods is recommended for developing next-generation MM force fields with improved accuracy.