Multipole-Based Force Fields from ab Initio Interaction Energies and the Need for Jointly Refitting All...

Area of Science:

• Computational Chemistry
• Molecular Modeling
• Force Field Development

Background:

• Distributed atomic multipole (MTP) moments offer more realistic electrostatic potential (ESP) reproduction than point charges (PCs).
• MTPs can capture anisotropic atomic properties, enhancing molecular force field capabilities.
• The quantitative improvement of MTPs over PCs in describing intermolecular interactions remains an open question.

Purpose of the Study:

• To investigate whether multipolar electrostatics in standard force fields quantitatively improve the reproduction of intermolecular interactions compared to point charges.
• To assess the impact of ESP-fitted MTPs and refitted Lennard-Jones (LJ) parameters on interaction energy accuracy.
• To determine the conditions under which atomic MTPs provide clear benefits for reproducing ab initio dimerization energies.

Main Methods:

• Characterization of interaction energies for benzonitrile (BZN) and formamide (FAM) homodimers across various conformations.
• Comparison of ESP reproduction accuracy between MTPs and PCs.
• Joint optimization of electrostatic (MTPs) and Lennard-Jones (LJ) parameters, including an exhaustive exponent scan for the LJ potential.

Main Results:

• While MTPs capture ab initio ESP an order of magnitude better than PCs, this does not directly translate to improved interaction energy calculations.
• Neither ESP-fitted MTPs nor refitted LJ parameters alone showed clear superiority of atomic MTPs.
• Joint optimization of MTPs and LJ parameters in nonpolarizable force fields demonstrated clear benefits.
• Atomic MTPs with a 9-6 LJ potential reproduced ab initio dimerization energies with ~30% less error than PCs with a 12-6 LJ potential (RMSD 0.13 vs 0.18 kcal/mol).
• The improvement using MTPs was more pronounced with a 9-6 LJ potential compared to a 12-6 LJ potential.

Conclusions:

• Atomic MTPs are beneficial for reproducing ab initio dimerization energies only when jointly optimized with LJ parameters within standard force fields.
• The combination of atomic MTPs and a 9-6 LJ potential offers a significant improvement over traditional point charge models for intermolecular interactions.
• Force field development should consider the coupled optimization of electrostatic and non-bonded parameters for enhanced accuracy.