Effect of the QM Size, Basis Set, and Polarization on QM/MM Interaction Energy Decomposition Analysis

Area of Science:

• Computational Chemistry
• Theoretical Chemistry
• Quantum Chemistry

Background:

• Accurate modeling of solvated systems is crucial in chemistry and biology.
• Quantum mechanics/molecular mechanics (QM/MM) methods are widely used for such studies.
• Understanding the convergence of interaction energy components with respect to the QM region size is vital for reliable QM/MM calculations.

Purpose of the Study:

• To investigate the impact of the quantum mechanics (QM) region size on the convergence of interaction energy components within QM/MM calculations using an electrostatic embedding scheme.
• To evaluate the performance of the QM/MM-EDA approach with atomic charges and dipoles for cationic, anionic, and neutral systems in a polar environment (water).
• To compare QM/MM-EDA results with pure quantum mechanical (QM) calculations and assess the benefits of including bulk solvation.

Main Methods:

• Application of an extended Energy Decomposition Analysis (EDA) scheme within QM/MM calculations with electrostatic embeddings (QM/MM-EDA).
• Inclusion of atomic charges and dipoles in the QM/MM-EDA framework.
• Systematic variation of the QM region size for cationic, anionic, and neutral systems interacting with a water environment.
• Comparison of QM/MM-EDA results with and without bulk solvent description using molecular mechanics (MM) potentials.

Main Results:

• Significant improvements in interaction energy components (electrostatic, Pauli, polarization) were observed when bulk solvent was included in the QM/MM-EDA scheme compared to pure QM calculations.
• The electrostatic interaction component requires surprisingly large QM regions for converged values, contrary to typical cluster models.
• Increasing the QM basis set or introducing MM polarization did not accelerate convergence with QM region size but improved the accuracy of energy components.

Conclusions:

• Converged electrostatic interaction energies in polar environments necessitate substantially larger QM regions than commonly used in cluster models.
• QM/MM-EDA with bulk solvent description offers significant advantages over pure QM calculations for solvated systems.
• The findings provide crucial insights for optimizing QM/MM embedding schemes and developing improved molecular mechanics force fields for solvated systems.