Is an Inductive Effect Explicit Account Required for Atomic Charges Aimed at Use within the Force Fields?

Area of Science:

• Computational Chemistry
• Molecular Modeling
• Quantum Chemistry

Background:

• Polarization and inductive effects are crucial in chemistry, yet polarization is prioritized in biomolecular modeling, while inductive effects are often neglected in force fields.
• Current molecular simulations predominantly use non-polarizable force fields, limiting accuracy.

Purpose of the Study:

• To investigate the significance of electronic effects, particularly the inductive effect, in atomic charge calculations.
• To establish a hierarchy of effects for improving molecular electrostatic potential (MEP) reproduction in force fields.

Main Methods:

• Evaluated atomic charge calculation models including formal charges, MMFF94 bond charge increments, Dynamic Electronegativity Relaxation (DENR), and RESP.
• Developed a scheme to estimate individual contributions of formal charge, nearest neighbors, inductive effect, and polarization.
• Compared residual MEP errors against quantum chemical reference data to assess the impact of each effect.

Main Results:

• Formal charges are most critical, followed by nearest neighbor effects.
• Explicitly accounting for the inductive effect significantly improves MEP reproduction, both qualitatively and quantitatively.
• The contribution of polarization effects was found to be surprisingly comparable in magnitude to inductive effects, even in systems where polarization is expected to dominate.

Conclusions:

• A clear hierarchy of electronic effects for atomic charge models has been established, highlighting the underappreciated importance of the inductive effect.
• Future force field development should incorporate explicit treatment of inductive effects for enhanced accuracy in molecular simulations.
• The findings suggest a need to re-evaluate the balance between inductive and polarization effects in computational chemistry models.